Reduction of scar formation in full-thickness wounds with topical celecoxib treatment

Adult wound repair occurs with an initial inflammatory response, reepithelialization, and the formation of a permanent scar. Although the inflammatory phase is often considered a necessity for successful adult wound healing, fetal healing studies have shown the ability to regenerate skin and to heal wounds in a scarless manner in the absence of inflammation. The cyclooxygenase-2 (COX-2) enzyme, a known mediator of inflammation, has been shown to contribute to a variety of inflammatory conditions and to the development of cancer in many organs. To examine the role of COX-2 in the wound healing process, incisional wounds were treated topically with the anti-inflammatory COX-2 inhibitor celecoxib. Acutely, celecoxib inhibited several parameters of inflammation in the wound site. This decrease in the early inflammatory phase of wound healing had a significant effect on later events in the wound healing process, namely a reduction in scar tissue formation, without disrupting reepithelialization or decreasing tensile strength. Our data suggest that in the absence of infection, adult wound healing is able to commence with decreased inflammation and that anti-inflammatory drugs may be used to improve the outcome of the repair process in the skin by limiting scar formation.     

SUICIDE ATTEMPT DUE TO METOCLOPRAMIDE-INDUCED AKATHISIA

Akathisia as a side-effect of metoclopramide has received increasing attention in consultation-liaison psychiatry in recent years. A case of metoclopramide-induced akathisia resulting in a suicide attempt is reported in order to highlight the suffering of such patients and the factors that lead to misdiagnosis.     

Psychosocial Factors and Prediction of Headaches in College Adults

The current study evaluated psychosocial variables that may contribute to the experience of headache in college adults. One hundred ninety-nine participants, 103 women and 96 men, completed head pain logs for 4 weeks after completing measures assessing psychosocial variables. Multiple regression analyses indicated that level of emotional functioning, perception of stress, and gender were predictive of future headache frequency, intensity, and duration. Family history and health habits did not predict headache activity. These findings are consistent with research investigating psychosocial variables and headache activity.     

Oral midazolam premedication for paediatric day case patients

Forty-nine children having day-stay surgical procedures were randomly assigned to receive oral midazolam 0.75 mg·kg^?1 or placebo in a double blind fashion. The child's level of anxiety was assessed before premedication using parental, child and observer scales. The child and observer anxiety scores were repeated in the anaesthetic room. Most children presented for anaesthesia in a calm state, irrespective of whether they had received midazolam. Parents tended to overestimate their child's level of anxiety. Observer anxiety scores reliably predicted behaviour during induction of anaesthesia in the absence of a sedative. Observer scores decreased in the midazolam group (P<0.02), but not in the placebo group, children below six years having the greatest decrease with midazolam. The median time to discharge from hospital was delayed by 30 min in the midazolam group (P<0.01). Children do not require routine sedative premedication for day case procedures, but oral midazolam is useful in producing calm behaviour in those children with high observer anxiety scores.     

Effects of risk-associated human dietary macrocomponents on processes related to carcinogenesis in human-flora-associated (HFA) rats

Dietary fat, beef protein and fibre have been shown to modulatecancer risk in humans and the present study examined the biologicaleffects in human-flora-associated (HFA) rats of altering intakelevels within the normal human range. Two control groups, oneHFA and the other germfree (GF), consumed a human diet low infat, fibre and beef for 4 weeks; three other groups consumedhuman diets similar except for independent 3-fold increasesin fat, beef protein or fibre. After 2 weeks on the diets, magneticallyrecoverable microcapsules were given orally to the rats andsubsequently recovered from the faeces to assess endogenouscross-linking agents. After 4 weeks, measurements were madeof gut microfloral enzyme activities, hepatic activation ofdietary mutagens and hepatic DNA adducts by ³²P-postlabelling.Activation in vitro of the dietary mutagens 2-amino-3-methyl-3H-imidazo[4,5-f]quinolline (IQ) and 2-amino-l-methyl-6- phenytimidazo[4,5-b]pyridine(PhIP) by hepatic S9, formation of endogenous hepatic DNA adductsin vivo and the ß-glucuronidase activity of caecalcontents were all increased in the sequence high fat > highfibre > high beef = control. Of the two DNA adducts foundin all HFA rats, only one was present in GF controls, indicatingthat the human gut microflora (subject to human dietary modulation)either releases a DNA-adducting product able to act outsidethe gastrointestinal tract, or stimulates the generation ofsuch a product by mammalian processes. Caecal nitrate reductaseactivity was highest in rats fed the high beef diet, whilstentrapment of cross-linking agents was highest in those fedthe high fibre diet. These results show that risk-related componentsof human diets interact with human gut microflora to modulatethe production of endogenous DNA-adducting and cross-linkingsubstances.     

Normothermic renal artery perfusion: A comparison of perfusates

Hypothermia and preservative perfusates have been used to decrease ischemic renal injury. This study was performed to identify the preservative function of perfusates independent of the effects of hypothermia. Rats underwent 45 minutes of renal ischemia. Rectal and renal parenchyma temperatures were monitored and maintained within 1° C of normal. Perfusates were University of Wisconsin solution (UW), Euro-Collins solution, normal saline solution, and Ringer's lactate solution. A nonperfused ischemic control and a nonischemic control group were also evaluated. Parameters evaluated included serum creatinine and blood urea nitrogen levels, renal ischemic injury grade, renal weight, and gross appearance of the injured kidney. Rats treated with UW solution were found to have a significantly lower creatinine, blood urea nitrogen, and injury grade than the other three perfused groups. The external gross appearance of the UW-treated kidneys was normal, whereas that of the other groups demonstrated moderate to severe injury. Although the mean right/left renal weight difference of the UW-treated group was lower than that of the other three groups, this was not statistically significant. Under normothermic conditions in rats, UW solution affords significant renal protection from ischemia. Euro-Collins, normal saline, and Ringer's lactate solutions display no significant protective effect.Presented at the Twentieth Annual Meeting of the Peripheral Vascular Surgery Society, New Orleans, La., June 10, 1995.     

A COMPARISON OF KETOPROFEN SR AND SULINDAC IN THE ELDERLY WITH RHEUMATOID ARTHRITIS

The elderly (age >65 years) are more vulnerable to side-effects induced by non-steroidal anti-inflammatory drugs (NSAIDs). We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis, 65 years of age or older. Sulindac was chosen because of its possible renal sparing effects, and ketoprofen SR because of its short half life and sustained release delivery system. Eighty patients were entered. More patients withdrew from the study due to side-effects in the sulindac group; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs, demonstrating that the elderly are susceptible to side-effects from NSAIDs.     

Intravenous Phenylephrine Preconditioning of Cardiac Grafts From Non–Heart-Beating Donors

Background. Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non-heart-beating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning.

Methods. Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non-heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 μg/kg (n = 7) before initiation of apnea. Non-heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia.

Results. Phenylephrine 25 μg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 ± 0.5 versus 7.7 ± 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 ± 5.3 versus 41.0 ± 3.4 mm Hg; p = 0.04). Phenylephrine 25 μg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09).

Conclusions. Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.