Local instillation of Staphylococcus aureus peptidoglycan at operation prevents wound healing impairment after trauma.

BACKGROUND: Considerable experimental evidence and limited clinical evidence indicate that wound healing is impaired after trauma. Because Staphylococcus aureus peptidoglycan (SaPG) accelerates healing in normal rats and prevents wound healing impairment induced by glucocorticoids, cyclophosphamide, and streptozotocin-diabetes, we hypothesized that SaPG would prevent the impaired wound healing after trauma. METHODS: In each of two experiments, 18 Sprague-Dawley male rats were divided into two groups, nine rats each, paired by weight; one group received unilateral comminuted femoral fracture and wounding (two dorsal skin incisions and six subcutaneous polyvinyl alcohol [PVA] sponges), and the other group was only wounded. The incision and PVA sponges on one side were inoculated at operation with saline (200 microL/incision, 50 microL/sponge) and on the other side with SaPG in saline (860 microg of SaPG per centimeter of incision, 0.5 mg of SaPG per sponge). Rats ate chow and drank tap water ad libitum and were killed 7 days postoperatively. RESULTS: In both experiments, the wound breaking strength (WBS) of saline-inoculated incisions was significantly lower in rats with femoral fracture; histologically, reparative granulation tissue was looser and less prominent. WBS of SaPG-inoculated incisions in rats with and without femoral fracture was significantly higher than that of saline-inoculated incisions and, histologically, reparative tissue was more prevalent, more closely packed, and more mature. WBS of SaPG-inoculated incisions in rats with femoral fracture was similar to that of saline-inoculated incisions in rats without femoral fracture. Reparative tissue hydroxyproline and histologic findings of saline-inoculated PVA sponge reparative tissue were similar in all rats, as were the increases induced by SaPG inoculation. CONCLUSION: Wound breaking strength and histologic findings of skin incisions (impaired in rats with unilateral femoral fracture) are more sensitive to the adverse effects of trauma than accumulation of PVA sponge reparative tissue. A single inoculation of SaPG at operation increased wound incision healing in rats both without and with femoral fracture and notably prevented the impaired healing in rats with femoral fracture.

Lethality of standard total parenteral nutrition following major liver resection in rats is prevented by high arginine and high branched chain amino acids but not by glutamine.

Standard total parenteral nutrition (TPN), with or without fat, in amounts approximating the ad libitum intake of normal rats is highly lethal for rats following 70% hepatectomy. Because of significant metabolic changes including alterations of branched chain amino acids (BCAA), arginine (ARG), and glutamine (GLN) associated with serious injury, sepsis, and liver dysfunction, we hypothesized that (1) increasing concentrations of BCAA and ARG in TPN and (2) including glutamine in the TPN may diminish the lethality. Male Sprague-Dawley rats with 70% hepatectomy and jugular vein catheterization were divided into groups. Two sets of experiments were conducted. In Experiment 1, the effects of varying concentrations of BCAA and ARG in the TPN infusate, singly and together, were assessed: Group 1, Standard TPN (19% BCAA, 4.8 g ARG/L); Group II, High BCAA TPN (35% BCAA, 4.8 g ARG/L); Group III, High ARG TPN (19% BCAA, 9.6 g ARG/L); Group IV, High ARG, High BCAA TPN (35% BCAA, 9.6 g ARG/L; Group V, chow and tap water ad libitum. In experiment 2, the effect of 2% GLN in TPN was evaluated: Group A, Standard TPN and Group B, 2% GLN TPN. All infusates were isocaloric (216 Kcal/Kg/d) and isonitrogenous (1.94 g N/Kg/d) delivered at half concentration on postoperative day 1, 3/4 concentration on postoperative day 2, and at full concentration thereafter. Experiment 1: Thirty-three to 36% of rats in Groups I (Standard TPN) (4/11), II (High BCAA TPN) (4/11) and III (High ARG TPN) (4/12) died within 6 days. In sharp contrast, none died in Groups IV (High BCAA, High ARG TPN) and V (rat chow and tap water) (P < 0.05 in each comparison). Among rats in the 4 TPN groups surviving 7 days, there were no significant differences in body weight change (minus 3-4%), spleen or lung weight, extent of liver regeneration (61-66%). Serum total protein and albumin were significantly higher in Group V (chow-fed) (similar to values in normal rats) than in Groups I-IV, P < 0.05 in each case. Serum total bilirubin was significantly higher in Group I than in normals and in Groups II, III, and V. Serum lactate dehydrogenase levels were similar in normals and all 5 groups. Serum aspartate amino transferase level was higher in Group I than in normals but not significantly different from those groups II-V; the latter were similar to normals. Experiment 2: Thirty percent of rats in Groups A (Standard TPN) (3/10) and B (GLN TPN) (3/10) died within 6 days. Among rats surviving for 7 days, body weight change (minus 3-5%), liver regeneration (67-70%), and liver tests were similar in both groups. TPN modified to contain high concentrations of both BCAA and ARG (but not of either alone) prevented the high frequency of lethality induced by standard TPN in rats with 70% hepatectomy. No such salutary effect was shown by modifying the TPN to contain 2% GLN. The striking benefit observed when TPN containing high BCAA and high ARG was infused may be due to the high BCAA leading toward normalization of serum amino acid levels, reducing proteolysis, increasing protein synthesis, and accelerating early liver regeneration, combined with the high ARG likely reducing serum ammonia and leading to increased host defense, and perhaps, thereby, preventing bacterial translocation and bacteremia.

Wound healing: captopril, an angiogenesis inhibitor, and Staphylococcus aureus peptidoglycan.

BACKGROUND: Captopril, an angiotensin-converting enzyme inhibitor, used for treating hypertension and heart failure, inhibits angiogenesis in the corneas of rats in response to basic fibroblast growth factor, slows the growth of experimental tumors in rats, and leads to the regression of Kaposi's sarcoma. Because angiogenesis is key to wound healing, we hypothesized that captopril would impair wound healing. We hypothesized also that because local application at operation of Staphylococcus aureus peptidoglycan (SaPG) increases angiogenesis and accelerates wound healing in rats, SaPG would prevent or ameliorate the postulated captopril-impaired wound healing. MATERIALS AND METHODS: In each experiment, rats were divided randomly into two groups: one drinking tap water, and the other, tap water containing 0.5 mg captopril/ml. All ate chow and drank ad libitum, pre-operatively (4-12 days) and postoperatively (7 days). In experiments 1 and 2, bilateral paravertebral 5.5-cm skin incisions were made aseptically (intraperitoneal sodium pentobarbital), and closed with interrupted No. 35 stainless-steel sutures. On one side, the wound was immediately inoculated with 157 microliter pyrogen-free isotonic saline and on the other side the wound was inoculated with 157 microliter saline containing 4.7 mg SaPG (860 microgram SaPG/cm incision). In the third experiment, polyvinyl alcohol (PVA) sponges (16-17 mg dry wt each) containing either 50 microliter saline or 0.5 mg SaPG in 50 microliter saline were implanted subcutaneously, two on each side, via 1-cm incisions closed with a single suture. In the fourth experiment, 5.5-cm bilateral skin incisions and subcutaneous implantation of PVA sponges were done as described but all sites were instilled with saline only. All rats were euthanized (CO(2) asphyxia) 7 days postoperatively. RESULTS: Wound breaking strength (WBS) of the saline-treated incisions was significantly higher (P < 0.001) in captopril-treated rats than in controls (172 +/- 13 g vs 105 +/- 6 g) in experiment 1 and higher, but not significantly in captopril-treated rats in experiment 2 (153 +/- 8 g vs 114 +/- 6 g) (PNS). SaPG inoculation of the incisions increased WBS significantly in both control and captopril-treated rats: 187 +/- 11 g vs 105 +/- 6 g (P < 0.001) and 283 +/- 16 g vs 172 +/- 13 g (P < 0.001), respectively, in experiment 1, and 217 +/- 13 g vs 114 +/- 6 g (P < 0.0001) (controls) and 266 +/- 17 g vs 153 +/- 8 g (captopril-treated rats) (P < 0.0001) in experiment 2. In experiment 3, subcutaneous PVA saline-inoculated sponge reparative tissue hydroxyproline (OHP) content was similar in control and captopril-treated rats, and SaPG inoculation increased reparative tissue OHP significantly in both groups: 2458 +/- 218 microgram/100 mg dry sponge vs 3869 +/- 230 microgram/100 mg (P < 0.001) (controls) and 2489 +/- 166 microgram/100 mg vs 4176 +/- 418 microgram/100 mg (P < 0.001) (captopril-treated rats). Histologically, angiogenesis and reparative tissue collagen were similar in control and captopril-treated rats, in both saline-inoculated and SaPG-inoculated sponges. In experiment 4 (all incisions and subcutaneous PVA sponges were saline-inoculated), there was no significant difference in WBS between control and captopril-treated rats (107 +/- 6 g vs 96 +/- 5 g, NS). PVA sponge reparative tissue OHP was significantly higher in captopril-treated rats: 3698 +/- 170 microgram/100 mg dry sponge vs 2534 +/- 100 microgram/100 mg (P < 0.0001). CONCLUSION: Unexpectedly, in four experiments, captopril did not inhibit WBS or PVA sponge reparative tissue angiogenesis or collagen accumulation; in fact, WBS was increased significantly in one of three experiments, and PVA sponge reparative tissue OHP was increased significantly in one of two experiments. Also, captopril did not interfere with the wound healing-accelerating effect of SaPG.

H(2)O(2) is an important mediator of physiological and pathological healing responses.

BACKGROUND: TGF-beta1 is a pleiotropic cytokine that plays a key role in wound healing and organ fibrosis. We have recently demonstrated that, in part, some fibrogenic actions of TGF-beta1 are mediated via formation of H(2)O(2). We have also demonstrated that TGF-beta1 plays a key role in the accelerated healing response induced by a peptidoglycan derived from some strains of Staphylococcus aureus (SaPG). METHODS: To investigate further the role of H(2)O(2) in healing responses, we implemented and improved a method to measure this reactive oxygen species. Using this method, we quantified the production of H(2)O(2) by cultured hepatic stellate cells-the main cells involved in type I collagen production in the liver-and by saline- and SaPG-inoculated polyvinyl alcohol sponges that had been surgically subcutaneously implanted in the dorsum of rats. RESULTS: We show that cultured hepatic stellate cells produce significant amounts of H(2)O(2). We show also that H(2)O(2) formation by saline- and SAPG-inoculated sponges is more intense during the early inflammatory phase of the healing response and precedes collagen deposition. Moreover, the production of H(2)O(2) is much higher in SaPG-inoculated sponges than in those inoculated with saline solution. CONCLUSIONS: Based on these findings, and on the fact that H(2)O(2) is produced during TGF-beta-induced upregulation of the alpha1(I) procollagen gene, we conclude that H(2)O(2) is one of the mediators of healing responses.

Does being a chief resident predict leadership in pediatric careers?

OBJECTIVE: Many organizations make efforts to identify future pediatric leaders, often focusing on chief residents (CRs). Identifying future leaders is an issue of great importance not only to the ultimate success of the organization but also to the profession. Because little is known regarding whether completing a CR predicts future leadership in medicine, we sought to determine if former pediatric CRs when compared with pediatric residents who were not CRs reported more often that they were leaders in their profession. DESIGN/METHODS: Twenty-four pediatric training programs stratified by resident size (<18, 18-36, and >36) and geography (East, South, Midwest, and West) were selected randomly from the Graduate Medical Education Directory (American Medical Association, Chicago, IL). Program directors were contacted by mail and telephone and asked to provide their housestaff rosters from 1965-1985. The resulting resident sample was surveyed by questionnaire in 1995. RESULTS: Fifteen of 17 program directors (88%) who possessed the requested data provided 1965-1985 rosters yielding a sample of 963 residents. Fifty-five percent of the resident sample (533) responded. Fifty-eight of the respondents had not completed a pediatric residency, leaving a survey sample of 475. Thirty-four percent (163) were CRs. The sample had a mean age of 47, 67% were male and 87% married. Fellowships were completed by 51%. More former CRs compared with non-CRs (75% vs 64%), more former fellows than non-fellows (75% vs 60%) and more males than females (74% vs 55%) reported they were professional leaders. These associations persisted in a logistic regression that controlled for CR status, gender, marital status, and fellowship status as leadership predictors. Former CRs, former fellows, and men were, respectively, 1.8, 2.3, and 2.3 times more likely to report professional leadership. CONCLUSIONS: Pediatric residents who were former CRs and/or fellows, and males were more likely to report professional leadership. Although men were more likely to report professional leadership, with more women entering pediatrics the reported gender differences will likely disappear over time.

Single local instillation of Staphylococcus aureus peptidoglycan prevents diabetes-induced impaired wound healing.

Diabetes-induced impaired wound healing is characterized by inhibition of the inflammatory response to wounding, macrophage infiltration, angiogenesis, fibroplasia, reparative collagen accumulation, and wound breaking strength. Because all of these processes are accelerated in normal rats by a single local application at operation of Staphylococcus aureus peptidoglycan, we hypothesized that S. aureus peptidoglycan would prevent diabetes-induced impaired wound healing, despite persistent, untreated hyperglycemia, polydipsia, glycosuria, and polyuria. Sprague- Dawley male rats were divided into two groups. One group received an intraperitoneal injection of streptozotocin (65 mg/kg) in citrate solution; the other group received an intraperitoneal injection of an equivalent volume of citrate solution. Seventeen days after the injections, the diabetic and control rats received aseptically two 5.5-cm paravertebral incisions and subcutaneous implantation of six polyvinyl alcohol sponges, three on each side. On one side, each sponge contained 0.5 mg S. aureus peptidoglycan in 50 microliter saline solution, and the incision was inoculated along its length with 4.7 mg S. aureus peptidoglycan in 157 microliter saline solution (860 microgram/S. aureus peptidoglycan/cm incision); on the other side, the same respective volumes of saline were used. During the preoperative and postoperative periods, diabetic rats lost a small amount of weight (2%), were hyperglycemic (363 +/- 10 mg/100 ml blood), polydipsic, glycosuric, and polyuric, whereas the controls gained weight (25%) and were normoglycemic (104 +/- 5 mg/100 ml blood); these differences were significantly different (p <.001 in each case). In controls, S. aureus peptidoglycan inoculation increased wound breaking strength (by a factor of 2.0) and hydroxyproline content (by a factor of 1.4; p <.001 in each case); in diabetics, there were significant decreases in wound breaking strength (by a factor of 1.7) and hydroxyproline content (by a factor of 1.3) of saline solution-inoculated incisions and sponges compared with the wound breaking strength and hydroxyproline content of saline solution-inoculated incisions and sponges in controls (p <.02 and p <.001, respectively). These decreases were completely prevented when the incisions and polyvinyl alcohol sponges had been inoculated at operation with S. aureus peptidoglycan; S. aureus peptidoglycan inoculation in the diabetic rats increased wound breaking strength by a factor of 2.2 and sponge reparative tissue hydroxyproline by a factor of 1.6 (p <.001 in each case). Thus, diabetes-induced impaired wound healing was prevented completely by a single local instillation at operation of S. aureus peptidoglycan, despite persistent, untreated hyperglycemia, polydipsia, polyuria, and glycosuria.

Nonviable Staphylococcus aureus and its peptidoglycan stimulate macrophage recruitment, angiogenesis, fibroplasia, and collagen accumulation in wounded rats.

We have previously shown that local application at the time of operation of Staphylococcus aureus, nonviable S. aureus, its cell wall, or S. aureus peptidoglycan accelerates wound healing. We hypothesized that this effect is due to both direct and indirect mechanisms, among which is an increase in the inflammatory response to wounding, resulting in an increase in macrophages, angiogenesis, and fibroblasts. Twenty-seven Sprague-Dawley male rats were anesthetized, and two 7-cm paravertebral skin incisions were made. Four polyvinyl alcohol sponges, two on each side, containing either 100 microliter of isotonic saline or 0.5 mg of nonviable S. aureus or S. aureus peptidoglycan in 100-microliter saline were implanted subcutaneously. Nonviable S. aureus or S. aureus peptidoglycan (860 microgram/cm incision) in 200-microliter saline were inoculated into the incisions at closure. The rats ate a commercial rat chow and drank tap water ad libitum throughout. After days 3 and 7 postwounding, rats were euthanized, and tissues were examined for immunohistochemical features of reparative tissue using ED-1, Factor VIII, and vimentin antibodies, markers for monocyte/macrophages, endothelial cells, and mesenchymal cells (including fibroblasts), respectively. Incisions treated with nonviable S. aureus or S. aureus peptidoglycan showed more macrophages along and deep in the wound tract 7 days postoperatively. Nonviable S. aureus or S. aureus peptidoglycan-treated sponges were surrounded and penetrated by much larger capsules of reparative tissue than saline-treated sponges at both 3 and 7 days. Neutrophil influx was much greater in nonviable S. aureus or S. aureus peptidoglycan-treated sponges, especially in central regions, and there were many more ED-1-stained macrophages in distinct geographic locations, specifically, the more peripheral-cortical areas. Some clustering of macrophages occurred around areas of invasion by reparative tissue into the surrounding subcutaneous fat and within the interstices of the sponges at the interface between reparative tissue and acute inflammatory cells. In contrast, saline-treated sponge reparative tissue had significantly fewer macrophages, much thinner and flimsy reparative tissue, with proportionately fewer macrophages clustering centrally. There were many more mesenchymal cells (notably fibroblasts) and new blood vessels and much more reparative collagen in the nonviable S. aureus or S. aureus peptidoglycan-treated sponges. We conclude that local application of nonviable S. aureus or S. aureus peptidoglycan at wounding induces an increased number and alteration in location of macrophages, increased influx (or proliferation) of mesenchymal cells (notably fibroblasts), and increased angiogenesis and reparative collagen accumulation, as well as increasing the overall acute inflammatory response to wounding.

Health status and practices of urban Caribbean Latinos with diabetes mellitus.

Although Caribbean Latinos are more likely than non-Hispanic whites to develop diabetes, their health status has been poorly characterized. Information on diabetes management, metabolic control, dietary habits, and diabetes knowledge was gathered from a group of urban Caribbean Latinos with diabetes in order to characterize the nutritional behaviors, diabetes attitudes, health perceptions, and metabolic control of this high risk group. Interviews and medical record reviews were conducted among seventy low-income urban Caribbean Latinos with type 2 diabetes mellitus. Patients attending outpatient clinics were interviewed by bilingual interviewers. Medical records were reviewed to ascertain prevalence of diabetes-related complications, medications, and metabolic parameters. Participants were primarily Spanish-speaking and of Puerto Rican origin. Eighty-one percent were unemployed, and only 27% had completed high school or higher educational levels. Average hemoglobin A1c was 10.6%. Among those with hypertension and hyperlipidemia, many were not receiving treatment. Participants' estimation of their own degree of metabolic control was poor, as was their understanding of desirable blood glucose and weight goals. A second evening meal was common. Diets were higher in fat and sugar content than currently recommended. More effective treatment strategies for both patients and providers are needed to improve glycemic control and cardiovascular risk factors among indigent urban Caribbean Latinos. Essential features of such strategies for patient programs include culturally appropriate dietary counseling and low literacy materials to better communicate glycemic and weight goals and dietary guidelines. Provider education is needed regarding established guidelines and cultural influences on diabetes-related practices.

Trillion virion delay: time from testing positive for HIV to presentation for primary care.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals' initial presentation to medical care frequently occurs at a point of advanced immunosuppression. OBJECTIVES: To investigate the time between HIV testing and presentation to primary care. Also to examine factors associated with delayed presentation. METHODS: One hundred eighty-nine consecutive outpatients without prior primary care for HIV infection were assessed at 2 urban hospitals: Boston City Hospital, Boston, Mass, and Rhode Island Hospital, Providence. Sociodemographics, alcohol and drug use, social support, sexual beliefs and practices, and HIV testing issues were examined in bivariate and multivariate analyses for association with delay in presentation to primary care after positive test results for HIV. RESULTS: Of 189 patients, 74 (39%) delayed seeking primary care for more than 1 year, 61 (32%) delayed for more than 2 years, and 35 (18%) for more than 5 years after an initial positive HIV serologic evaluation. The median CD4+ cell count of subjects was 0.28 x 10(9)/L (range, 0.001-1.71 x 10(9)/L). In multiple linear regression analysis the following characteristics were found to be associated with delayed presentation to primary care after HIV testing: history of injection drug use (P<.001); not having a living mother (P=.01); not having a spouse or partner (P=.08); not being aware of HIV risk before testing (P<.001); and being notified of HIV status by mail or telephone (P=.002). An interaction effect between sex and screening for alcohol abuse was significant (P=.03) and suggested longer delays for men with positive screening test results (CAGE [an alcoholism screening questionnaire containing 4 structured questions], 2+) compared with men without positive screening test results or women. CONCLUSIONS: Patients with positive HIV test results often delay for more than a year before establishing primary medical care. Information readily available at the time of HIV testing concerning substance abuse, social support, and awareness of personal HIV risk status is useful in identifying patients who are at high risk of not linking with primary care. Patients who were notified of their HIV status by mail or telephone delayed considerably longer than those notified in person. Efforts to ensure primary care linkage at the time of notification of positive HIV serostatus are necessary to maximize benefits for both individual and public health and should be an explicit task of posttest counseling.

Sexual ethics. Disclosure of HIV-positive status to partners.

OBJECTIVE: To determine factors associated with disclosure of human immunodeficiency virus (HIV)-positive status to sexual partners. METHODS: We interviewed 203 consecutive patients presenting for primary care for HIV at 2 urban hospitals. One hundred twenty-nine reported having sexual partners during the previous 6 months. The primary outcome of interest was whether patients had told all the sexual partners they had been with over the past 6 months that they were HIV positive. We analyzed the relationships between sociodemographic, alcohol and drug use, social support, sexual practice, and clinical variables; and whether patients had told their partners that they were HIV positive was analyzed by using multiple logistic regression. RESULTS: Study patients were black (46%), Latino (23%), white (27%), and the majority were men (69%). Regarding risk of transmission, 41% were injection drug users, 20% were homosexual or bisexual men, and 39% were heterosexually infected. Sixty percent had disclosed their HIV status to all sexual partners. Of the 40% who had not disclosed, half had not disclosed to their one and only partner. Among patients who did not disclose, 57% used condoms less than all the time. In multiple logistic regression analysis, the odds that an individual with 1 sexual partner disclosed was 3.2 times the odds that a person with multiple sexual partners disclosed. The odds that an individual with high spousal support disclosed was 2.8 times the odds of individuals without high support, and the odds that whites or Latinos disclosed was 3.1 times the odds that blacks disclosed. CONCLUSIONS: Many HIV-infected individuals do not disclose their status to sexual partners. Nondisclosers are not more likely to regularly use condoms than disclosers. Sexual partners of HIV-infected persons continue to be at risk for HIV transmission.

Buena Alimentacion, Buena Salud: a preventive nutrition intervention in Caribbean Latinos with type 2 diabetes.

A culturally sensitive 3-month intervention was provided to 18 Caribbean Latino men and women with non-insulin-dependent (type 2) diabetes mellitus. Compared to the randomly assigned control group, the intervention group showed statistically significant decreases in total calories, fat calories, percent of calories from fat, saturated fat calories, and percent of calories from saturated fat The intervention group showed increases in calories from carbohydrates and in the percent of calories from fiber.

Sunbathing habits and sunscreen use among white adults: results of a national survey.

OBJECTIVES: This study assessed current levels of sunbathing and sunscreen use in the United States. METHODS: From a general-population telephone survey of aquatic activities among adults in 3042 US households, we examined responses by the 2459 Whites. RESULTS: Most adults (59%) reported sunbathing during the past year, and 25% reported frequent sunbathing. Of the subsample who reported sunbathing during the month before the interview, 47% routinely used sunscreen. Of these individuals, almost half did not use sunscreens with a solar protection factor of 15 or higher. CONCLUSIONS: About a quarter of US White adults report frequent sunbathing, and only about a quarter of sunbathers use sunscreens at recommended levels. These results should help focus future sun protection educational efforts.

Contrasting effects of identical nutrients given parenterally or enterally after 70% hepatectomy: bacterial translocation.

High mortality occurs in rats with 70% hepatectomy fed intravenous (IV) total parenteral nutrition (TPN; 13.9% glucose, 4.17% amino acids, 1.46% fat, electrolytes, trace minerals, and vitamins providing 216 kcal.kg-1.d-1) but not when the identical nutrients are given at the same rate enterally (gastrostomy). We hypothesized that a difference in bacterial translocation (BT) was a contributing factor to this phenomenon. Forty-five male Sprague-Dawley rats (300-360 g) were divided into five groups and underwent the following: control (no operation), sham (intraperitoneal [IP] pentobarbital anesthesia, central venous and gastrostomy catheters, laparotomy, sham hepatectomy), standard oral feeding (SOF), TPN (IV nutrients), and total enteral nutrition (TEN; gastrostomy). The SOF, TPN, and TEN groups had IP pentobarbital anesthesia, central venous and gastrostomy catheters, and 70% hepatectomy. Postoperatively, control and SOF (both catheters plugged) rats ate a commercial rat chow and drank tap water ad libitum pre- and postoperatively. The sham, TPN, and TEN groups were given the identical infusate composition as above, but the nutrient concentrations were cut in half (110 kcal/kg) and three-quarters (165 kcal/kg) on postoperative days 1 and 2, respectively. At the end of postoperative day 2, all rats were euthanized. BT to mesenteric lymph nodes (MLNs), liver, spleen, and lungs was significantly higher in the TPN rats compared with all other groups, except that BT to the MLNs was similar in the TPN and TEN groups. Bacteremia was found only in the TPN rats. BT in TPN rats with 70% hepatectomy was significantly greater 48 h after operation than in those fed the identical nutrients enterally at the same rate; this correlates with the previously reported significantly greater mortality in rats with 70% hepatectomy receiving TPN.

Wound fluids from saline solution- and Staphylococcus aureus peptidoglycan-inoculated sponges induce expression of matrix metalloproteinase 13 messenger ribonucleic acid by cultured rat fibroblasts.

Polyvinyl alcohol sponges inoculated with Staphylococcus aureus peptidoglycan induce an accelerated wound healing response when implanted subcutaneously in rats. S. aureus peptidoglycan leads to a marked increase (50%) in reparative tissue collagen (as measured by hydroxyproline) by 4 days. However, this effect drops by 7 days and by 14 days; hydroxyproline levels are similar in sponges inoculated with S. aureus peptidoglycan or saline solution. These data suggest a very active early remodeling process in S. aureus peptidoglycan sponge reparative tissue. Consistent with this observation, we had found that steady-state levels of matrix metalloproteinase-13 mRNA were higher and persisted longer in S. aureus peptidoglycan sponge reparative tissue than in controls. We hypothesized that S. aureus peptidoglycan might induce a change in reparative tissue fibroblast phenotype or modify the character of the wound fluid. Fibroblasts obtained from saline solution- and S. aureus peptidoglycan-inoculated sponges 4 days after subcutaneous implantation and cultured in Eagle's minimal essential medium supplemented with 10% fetal calf serum were similar with respect to morphologic features, proliferation, and expression of pro alpha1 (I) and alpha1 (III) collagens and tissue inhibitor of metalloproteinase-1 mRNA by Northern blot analysis. Neither cell type expressed matrix metalloproteinase-13 mRNA. No changes in the above parameters were detected when such fibroblasts were cultured for 24 hours in the presence of 0.5 mg of S. aureus peptidoglycan per 10 ml of medium or with fluid obtained from control sponges cultured for 12 hours with phosphate-buffered saline solution. Wound fluids extracted with Eagle's minimal essential medium by homogenization of saline solution- and S. aureus peptidoglycan-inoculated sponges implanted subcutaneously for 12 hours did not affect the proliferation of the fibroblasts. However, the extracts had a profound effect on the cellular expression of tissue inhibitor of metalloproteinase-1, matrix metalloproteinase-13, and pro alpha1 (I) collagen mRNA. Specifically, expression of matrix metalloproteinase-13 mRNA was induced, expression of pro alpha1 (I) collagen mRNA was reduced by 70%, and expression of tissue inhibitor of metalloproteinase-1 mRNA was increased by 150%. These changes were the same irrespective of whether the wound fluid was obtained from saline solution- or S. aureus peptidoglycan-inoculated sponges. Fluid obtained from S. aureus peptidoglycan-inoculated sponges, which contain a greater inflammatory exudate than saline solution-inoculated sponges do, is enriched in matrix metalloproteinase-13 mRNA-inducing activity. The nature of the factor(s) that induces matrix metalloproteinase-13 mRNA expression is not known. However, preliminary data suggest that the matrix metalloproteinase-13-inducing factor(s) is heterogeneous with regard to size and is temperature sensitive and trypsin resistant.

Staphylococcus aureus peptidoglycan ameliorates cyclophosphamide-induced impairment of wound healing.

Cyclophosphamide given systemically to rats leads to impaired wound healing, characterized by decreases in the inflammatory reaction, fibroplasia, neovascularization, reparative collagen accumulation, and wound breaking strength. In contrast, the local application of Staphylococcus aureus peptidoglycan at the time of wounding increases all of these processes in normal rats. Accordingly, we hypothesized that inoculation of S. aureus peptidoglycan into wounds of cyclophosphamide-treated rats would ameliorate the otherwise impaired healing. Dorsal bilateral skin incisions and subcutaneous implantation of polyvinyl alcohol sponges (two on each side) were performed on male Sprague-Dawley rats receiving either saline or cyclophosphamide (24 mg/kg) intraperitoneally at the time of operation, on postoperative days 1, 2, 3, 4 (for rats killed on postoperative day 7), and also on day 8 (for rats killed on postoperative day 14). The incisions on one side were inoculated at the time of closure with 0.2 ml of saline solution, and the incisions on the other side with 6 mg S. aureus peptidoglycan in 0.2 ml saline solution (860 microg/cm incision). The sponges were instilled with 0.1 ml saline solution on the saline solution-instilled incision side or with S. aureus peptidoglycan 0.5 mg/sponge) in 0.1 ml saline solution on the other side. In control rats receiving saline solution intraperitoneally, incisions treated with S. aureus peptidoglycan were significantly stronger than saline solution-treated incisions by a factor of 1.8 at 1 week (p < 0.001); at 2 weeks the increase was small and not significant. Cardiac blood leukocytes and platelets fell markedly (90%) in cyclophosphamide- treated rats, and there was a decrease in wound breaking strength of their saline-treated incisions at both 7 and 14 days compared with saline solution-treated incisions of control rats. S. aureus peptidoglycan treatment of the wounds completely prevented this effect at 7 days, and partially at 14 days. Polyvinyl alcohol sponge reparative tissue hydroxyproline, 7 days after surgery, was decreased in cyclophosphamide-treated rats; this was completely prevented by S. aureus peptidoglycan treatment of the sponges. Histologically, the inflammatory response to the wounding, influx of macrophages and fibroblasts, angiogenesis, and collagen accumulation were all reduced at day 7 and 14 after surgery in the sponge reparative tissue of cyclophosphamide- treated rats; this was prevented by S. aureus peptidoglycan treatment of the sponges. In conclusion, a single local application of S. aureus peptidoglycan ameliorates cyclophosphamide-impaired wound healing.

Accelerating effects of nonviable Staphylococcus aureus, its cell wall, and cell wall peptidoglycan.

We have previously reported that local application of viable Staphylococcus aureus dramatically accelerates wound healing, but viable Staphylococcus epidermidis does not. Because the S. aureus effect occurred in the absence of infection and because the cell walls of the two bacterial species differ, we hypothesized that nonviable S. aureus, its cell wall, and its cell wall component(s) would accelerate healing. Nonviable S. aureus was prepared by chemical and physical means, and its cell wall and peptidoglycan was prepared from heat-killed cultures. In a large number of experiments, nonviable S. aureus (independent of the strain's protein A content), its cell wall, and peptidoglycan when instilled locally at the time of wounding each significantly increased the breaking strength of rat skin incisions (tested both in the fresh state and after formalin fixation). These agents also enhanced subcutaneous polyvinyl alcohol sponge reparative tissue collagen accumulation, generally by a factor of two. Histologic features of treated and control incisions were similar. In contrast, the reparative tissue of treated sponges contained more neutrophils, macrophages, capillaries, and collagen. These experimental data thus confirm our previous studies, as well as our hypothesis, and extend these observations of enhanced wound healing to specific fractions of the bacterial cell wall.

Traumatic pancreatitis: method and effects of i.v. fluids and Sandostatin.

UNLABELLED: Somatostatin and its analogs are used clinically to treat patients with pancreatitis. To evaluate the effects of i.v. Sandostatin (SNST) on rats with trauma-induced acute pancreatitis, 130 male Sprague-Dawley rats (300-350 g) underwent celiotomy, controlled direct pancreas contusion, and central i.v. line insertion under ip sodium pentobarbital anesthesia. The rats were divided randomly into control (IA, IIA, and IIIA) and SNST-treated (IB, IIB, and IIIB) groups. The basic infusion solution contained 4.8% glucose, vitamins, and electrolytes. For groups IA and IB, the infusion rate was 24 ml/kg/day, while it was 240 ml/kg/day for groups IIA, IIB, IIIA, and IIIB. SNST administration was 6 micrograms/kg/hr i.v. for groups IB and IIB during the first postoperative day, while group IIIB received 6 micrograms/kg/hr i.v. for 4 days. Surviving rats were euthanized after 4 days. All survivors and nonsurvivors were autopsied. In all groups, severity of pancreatitis, fat necrosis, and ascites were greater in the nonsurvivors (P < 0.005 in each case). Mortality rates were consistently lower in the SNST groups: IA (76%) vs IB (52%), IIA (71%) vs IIB (50%), and IIIA (63%) vs IIIB (50%). Because individual group mortality rates were not affected by volume of infusate given or length of time SNST was administered, the results of all control and all SNST rats were combined; there was a statistically significant lower mortality in the SNST-treated rats (51 vs 71%, P < 0.04). CONCLUSION: Intravenous administration of Sandostatin to rats following induction of severe acute traumatic pancreatitis significantly ameliorates the course of the disease.

Housing subsidies and pediatric undernutrition.

OBJECTIVE: To test the hypothesis that receipt of housing subsidies by poor families is associated with improved nutritional status of their children. DESIGN: Cross-sectional study. SETTING: Pediatric emergency department of an urban municipal hospital. PATIENTS: Convenience sample of 203 children younger than 3 years and their families who were being seen during one of twenty-seven 24-hour periods. MAIN OUTCOME MEASURES: Anthropometric indicators (z scores of weight for age, weight-for-height, and height-for-age), and the proportion of children with low growth indicator (weight-for-height below the 10th percentile or height-for-age below the fifth percentile, or both, of the reference population). RESULTS: Multivariate analysis controlling for demographics and program participation showed that receipt of housing assistance contributed significantly to z scores for weight-for-age (P = .03) and weight-for-height (P = .04). The risk of a child's having low growth indicators was 21.6% for children whose families were on the waiting list for housing assistance compared with 3.3% for those whose families received subsidies (adjusted odds ratio = 8.2, 95% confidence interval = 2.2 to 30.4, P = .002) CONCLUSION: Receiving a housing subsidy is associated with increased growth in children from low-income families, an effect that is consistent with a protective effect of housing subsidies against childhood undernutrition.

Assessment of compliance with home cardiorespiratory monitoring in infants at risk of sudden infant death syndrome. Collaborative Home Infant Monitoring Evaluation (CHIME).

OBJECTIVES: Documented monitoring was used to evaluate prospectively (1) the level of compliance among infants in whom cardiorespiratory monitoring was clinically indicated and (2) factors that might influence compliance: diagnosis, socioeconomic status, maternal age and education, and alarms. STUDY DESIGN: Sixty-seven infants (51% female, 49% term) were sequentially enrolled, and monitoring was prescribed for the following indications: siblings of sudden infant death syndrome victims (16%), apnea of prematurity (45%), and apparent life-threatening events or apnea of infancy (39%). Demographic data, alarm and event data, and a summary report of monitor use from the first monitor download were obtained. RESULTS: Maternal age, education, and insurance status did not differ significantly by indication for monitoring. The median number of monitor alarms per 10 hours of use was 0.7 for apnea or bradycardia and 0.6 for loose lead alarms. Monitors were available for use in the home from 2 to 106 days (median, 11 days). Median hours of monitor use per full day in the home was 15.5 hours. Of 67 infants, 58 used the monitor for at least part of every day in the home. The number of hours of monitor use per day did not differ significantly by diagnostic category, chronologic age, alarms, maternal age, education, or insurance type. This study population of infants at increased risk of sudden infant death syndrome had excellent compliance; 75% of the infants were monitored more than 10.5 hours per day, and 25% were monitored more than 21 hours per day. CONCLUSIONS: Documented monitoring provides an objective measure of compliance. These data provide a potential goal for level of compliance with home cardiorespiratory monitoring.