Preventing community-wide transmission of Cryptosporidium: a proactive public health response to a swimming pool-associated outbreak--Auglaize County, Ohio, USA.

The incidence of recreational water-associated outbreaks in the United States has significantly increased, driven, at least in part, by outbreaks both caused by Cryptosporidium and associated with treated recreational water venues. Because of the parasite's extreme chlorine tolerance, transmission can occur even in well-maintained treated recreational water venues (e.g. pools) and a focal cryptosporidiosis outbreak can evolve into a community-wide outbreak associated with multiple recreational water venues and settings (e.g. childcare facilities). In August 2004 in Auglaize County, Ohio, multiple cryptosporidiosis cases were identified and anecdotally linked to pool A. Within 5 days of the first case being reported, pool A was hyperchlorinated to achieve 99·9% Cryptosporidium inactivition. A case-control study was launched to epidemiologically ascertain the outbreak source 11 days later. A total of 150 confirmed and probable cases were identified; the temporal distribution of illness onset was peaked, indicating a point-source exposure. Cryptosporidiosis was significantly associated with swimming in pool A (matched odds ratio 121·7, 95% confidence interval 27·4-∞) but not with another venue or setting. The findings of this investigation suggest that proactive implementation of control measures, when increased Cryptosporidium transmission is detected but before an outbreak source is epidemiologically ascertained, might prevent a focal cryptosporidiosis outbreak from evolving into a community-wide outbreak.

Glucose-6-phosphate dehydrogenase activity in male premature and term neonates.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) activity is higher in term neonates than in adults. Some studies have suggested that activity may be even higher in preterm infants. OBJECTIVES: To determine if G6PD activity is higher in preterm than term neonates, and whether higher activity would interfere with diagnosis of G6PD deficiency in premature infants. METHODS: G6PD activity was determined in the first 48 hours after delivery in male premature, term, and near term infants. G6PD deficient neonates were separated, and the remaining premature infants compared with healthy, male, G6PD normal, near term and term neonates. RESULTS: Ninety four premature infants (mean (SD) gestational age 31.9 (3.8) weeks (range 23-36)) were studied. In four, G6PD activity was 0.8-1.8 U/g haemoglobin (Hb), which is clearly in the deficient range with no overlap into the normal range. G6PD activity in the remaining premature infants was significantly higher than in 24 near term and term neonates (gestational age > or = 37 weeks) (14.2 (4.6) v 12.0 (3.8) U/g Hb). Further analysis showed that significance was limited to those born between 29 and 32 weeks gestation, in which group G6PD activity was significantly higher than in those born before 29 weeks gestation, at 33-36 weeks gestation, and > or = 37 weeks gestation. CONCLUSIONS: G6PD activity is higher in premature infants born between 29 and 32 weeks gestation than in term neonates. This did not interfere with diagnosis of G6PD deficiency.

Protective effect of bilirubin in ischemia-reperfusion injury in the rat intestine.

BACKGROUND: Although bilirubin, which crosses the blood-brain barrier, can cause irreversible brain damage, it also possesses antioxidant properties that may be protective against oxidative stress. Intestinal ischemia-reperfusion (IR) injury results in cell destruction, mediated via the generation of reactive oxygen species. Although increased serum bilirubin is correlated with increased antioxidant potential in the face of hyperoxia, evidence of bilirubin-associated protective effect against IR injury remains nonspecific. We therefore sought to investigate whether hyperbilirubinemia would be protective against IR injury to the intestine. METHODS: Young adult rats were randomly assigned to one of three groups: 1) IR/control (n = 12); 2) IR/hyperbilirubinemia (n = 10), in which IR was generated while the rats were treated with a continuous infusion of bilirubin; and 3) hyperbilirubinemia controls (n = 10). Blood and intestinal tissue samples were obtained to determine serial thiobarbituric acid reducing substances (index of lipid peroxidation) and for xanthine oxidase/xanthine dehydrogenase and glutathione/glutathione disulfide ratios. Intestinal histopathology was graded from 1 (normal) to 4 (severe necrotic lesions). RESULTS: Histopathologic scoring and circulating and tissue thiobarbituric acid reducing substances were highest in the IR/control animals compared with either the IR/hyperbilirubinemics or the controls. All of these are consistent with the most severe injury in this group. Xanthine oxidase/xanthine dehydrogenase ratios were not significantly different among the groups. CONCLUSION: Hyperbilirubinemia ameliorates the extent of intestinal IR injury in our model and appears to act as an antioxidant. This study supports the concept that bilirubin possesses some beneficial properties in vivo, although no direct clinical conclusions can be drawn from these data.

Processing in the C-terminal domain of minicollagen XII removes a heparin-binding site.

A minicollagen comprising the two C-terminal domains of collagen XII (COL1 and NC1) has been expressed in insect cells and characterized biochemically. An interaction with heparin is demonstrated, which depends on the correct folding of the molecule. After secretion, minicollagen XII is immediately processed to a form lacking heparin binding ability. Processed and unprocessed trimers differ only at the level of the eight or nine C-terminal residues but they reveal different structures as judged from rotary shadowing images. Similar processing is also observed in the medium of transfected human HeLa cells. These data show that a heparin-binding site is present in the C-terminal end of the chicken collagen XII sequence and strongly suggest that proteolytic processing in the NC1 domain can occur in vivo and regulate the interactive properties of collagen XII.

Complete phalloplasty using the free radial forearm flap for correcting micropenis associated with vesical exstrophy.

PURPOSE: We present a new surgical technique for reconstructing the penis in a man with micropenis associated with vesical exstrophy. MATERIALS AND METHODS: A free radial forearm flap was used to create a penis of normal length and diameter. The flap was wrapped around the native micropenis. A penile prosthesis was then inserted in the flap to provide erection. RESULTS: The flap was well vascularized and no skin damage was observed 6 years after reconstruction. The patient achieved sexual intercourse on a regular basis. He is satisfied with the result. CONCLUSIONS: Free transfer of the radial forearm flap may be done in select men with micropenis associated with vesical exstrophy for penile reconstruction. An inflatable prosthesis may be inserted in the flap to provide erection. The results of this technique have remained stable in the long term. This method provides a new tool for phalloplasty in these difficult cases.

Collagenous sequence governs the trimeric assembly of collagen XII.

A minicollagen containing the COL1 and NC1 domains of chicken collagen XII has been produced in insect cells. Significant amounts of trimers contain a triple-helical domain in which the cysteines are not involved in inter- but in intrachain bonds. In reducing conditions, providing that the triple-helix is maintained, disulfide exchange between intra- and interchain bonding is observed, suggesting that the triple-helix forms first and that in favorable redox conditions interchain bonding occurs to stabilize the molecule. This hypothesis is verified by in vitro reassociation studies performed in the presence of reducing agents, demonstrating that the formation of interchain disulfide bonds is not a prerequisite to the trimeric association and triple-helical folding of the collagen XII molecule. Shortening the COL1 domain of minicollagen XII to its five C-terminal GXY triplets results in an absence of trimers. This can be explained by the presence of a collagenous domain that is too short to form a stable triple-helix. In contrast, the presence of five additional C-terminal triplets in COL1 allows the formation of triple-helical disulfide-bonded trimers, suggesting that the presence of a triple-helix is essential for the assembly of collagen XII.

Munchausen syndrome.

Munchausen syndrome is a rare condition in which the patient repeatedly seeks medical care for factitious illnesses. With this self-inflicted disease, the patients characteristically travel from one hospital to another, feigning acute, usually spectacular illnesses. The patients willingly submit themselves to extensive as well as invasive diagnostic and therapeutic procedures. Munchausen syndrome is a psychiatric disorder that requires psychiatric treatment. Reconstructive surgical procedures may be required to correct the acquired deformities. The difficulty in Munchausen syndrome lies essentially in early recognition of the psychiatric syndrome. Two exceptional cases are reported, and diagnosis and treatment are presented in the light of the current literature.

Negative side-effects of retention sutures for abdominal wound closure. A prospective randomised study.

OBJECTIVE: To assess the effect of retention sutures on the postoperative course of patients after major abdominal operations. DESIGN: Prospective, randomised study. SETTING: Teaching hospital, Germany. SUBJECTS: 95 patients who were at increased risk of wound failure after major abdominal operations. INTERVENTION: Conventional mass closure either with (n = 44) or without (n = 51) reinforcement by wire retention sutures. MAIN OUTCOME MEASURES: Pain intensity on postoperative days 3, 6, 9, and 12, patients' acceptance, retention-suture-related morbidity, general morbidity. RESULTS: Postoperative pain was overall more severe with retention sutures. On day 6, 31/49 control patients but only 13/41 patients with retention sutures were pain-free (p = 0.003, 95% CI 0.12 to 0.51). Twelve of 44 patients with retention sutures developed local complications of the sutures, and 21 of the 44 had to have them removed prematurely, in most cases because of intolerable pain. CONCLUSIONS: Retention sutures used to close abdominal wounds cause inconvenience, pain, and specific morbidity.

Amelioration of ischemia-reperfusion injury in rat intestine by pentoxifylline-mediated inhibition of xanthine oxidase.

BACKGROUND: Intestinal ischemia-reperfusion (IR) injury results in cell destruction, which may be mediated by the generation of reactive oxygen species, potentially toxic metabolites of xanthine oxidase. Pentoxifylline (PTX) possesses a variety of biochemical and antioxidant properties that can improve capillary flow and tissue oxygenation. Because of these combined effects, it has been hypothesized that pentoxifylline would protect against intestinal IR. METHODS: Young adult rats were randomly assigned to one of four experimental groups: IR/Placebo (n = 12) in which superior and inferior mesenteric arteries were clamped for 45 minutes and then reopened; IR/PTX (n = 11) in which IR was induced as in the Placebo group, but with 25 mg/kg PTX at 0, 30, and 60 minutes; No IR/Placebo (n = 12); and No IR/PTX (n = 6) in which placebo and PTX were applied with no IR. Blood and intestinal samples were taken for serial thiobarbituric acid-reducing substances (TBARS; index of lipid peroxidation), for xanthine oxidase-xanthine dehydrogenase ratios, glutathione, myeloperoxidase, and histopathology. RESULTS: Animals in the IR/PTX group had lower TBARS and the least severe histopathologic injury. Xanthine oxidasexanthine dehydrogenase ratios were elevated only in IR/ Placebo (0.67+/-0.22 vs. 0.45+/-0.14 in IR/PTX; 0.42+/-0.22 in No IR/Placebo; and 0.40+/-0.11 in No IR/PTX; p = 0.0009). Reduced glutathione was diminished in IR/PTX animals (38.9 +/-1.35 vs. 46.1+/-7.0 in IR/Placebo; 41.1+/-2.5 in No IR/ Placebo; 43.6+/-1.0 in No IR/PTX; p = 0.048). No differences were recorded in myeloperoxidase levels among groups. CONCLUSIONS: Pentoxifylline ameliorates histopathologic signs of injury and decreases lipid peroxidation (TBARS). Normal xanthine oxidase-xanthine dehydrogenase ratios in the treated compared with IR-only animals imply that the protective effect of PTX is at least partially mediated through inhibition of xanthine oxidase.

Circumferential torsoplasty.

Abdominoplasty procedures are often unsatisfactory in correcting body deformities remaining after massive weight loss. Lateral flanks, hip rolls and buttock ptosis need also to be addressed surgically. To achieve a more noticeable improvement in body contour, a circumferential torsoplasty procedure was performed in 30 patients during the years 1993-1997. Twenty of them had had a gastroplasty procedure before with a mean weight loss of 49.5 kg. Mean operative time was 210 min (range 150-420 min). The total resection weight ranged from 2 to 8.96 kg (mean 4.3 kg). Mean operative blood loss was 635 ml (range 300-1900 min). The mean hospital stay was 12 days. Minor complications occurred in four patients and major complications in one. Both patients and surgeons considered the outcome very satisfactory.

Free-flap evolution after hyperthermic regional chemotherapy in the isolated limb for malignant melanoma.

Two patients presenting with a stage I melanoma of the sole of the foot (Clark's level IV, Breslow's 2.8 mm, and Clark's level IV, Breslow's 3.2 mm) underwent a 3-cm tumor free-margin skin resection, followed by microanastomosed muscle flap reconstruction (serratus anterior and latissimus dorsi). Immediately after primary wound healing, an elective inguino-iliac lymph-node dissection, followed by hyperthermic isolated regional chemotherapy with Melphalan, was carried out. Only moderate swelling of both free flaps was observed after these procedures, and this resolved rapidly. The patients returned to ambulation after 2 weeks. No other side effects of the hyperthermic isolated regional chemotherapy were observed in the previously microanastomosed flaps.

Structural requirements for fibromodulin binding to collagen and the control of type I collagen fibrillogenesis--critical roles for disulphide bonding and the C-terminal region.

Fibromodulin belongs to the family of small, leucine-rich proteoglycans which have been reported to interact with collagens and to inhibit type I collagen fibrillogenesis. Decorin and fibromodulin exhibit a noticeable degree of sequence similarity. However, as previously reported [Font, B., Eichenberger, D., Rosenberg, L. M. & van der Rest, M. (1996) Matrix Biol. 15, 341-348] the domains of these molecules implicated in the interactions with type XII and type XIV collagens are different, these being the dermatan sulphate/chondroitin sulphate chain for decorin and the core protein for fibromodulin. At the present time the fibromodulin domains implicated in the interactions with fibrillar collagens remain unknown. In experiments reported here, we have sought to identify the structural requirements for fibromodulin interaction with collagen and for the control of type I collagen fibrillogenesis. Circular dichroism spectra and fibrillogenesis inhibition studies show that fibromodulin structure and its collagen fibrillogenesis control function are strictly dependent on the presence of intact disulphide bridge(s). In addition, we show that the binding of fibromodulin (or fibromodulin-derived fragments) to type I collagen is not necessarily correlated with fibrillogenesis inhibition. To isolate fibromodulin domains, the native proteoglycan was submitted to mild proteolysis. We have isolated an alpha-chymotrypsin-resistant fragment which contains the bulk of the N-terminal and central region of the molecule including the leucine-rich repeats 4 and 6 reported for decorin to be involved in type I collagen binding. This fragment does not bind to type I collagen. Using enzymes with different specificities, a number of large fragments of fibromodulin were obtained, suggesting a compact structure for this molecule which is relatively resistant to proteolysis. None of these N-glycosylated fragments were able to bind to type I collagen in co-sedimentation experiments. Taken together these results suggest that fibromodulin-type I collagen interactions leading to fibrillogenesis inhibition require more than one binding domain. One of these domains could be the C-terminal end of the molecule containing the disulphide loop which is absent in the chymotrypsin-resistant fragment.

Traumatic spinal accessory nerve palsy.

Spinal accessory nerve sections due to a purely traumatic origin are very rare. The authors report a case in which a total section of the spinal accessory nerve was observed after a glass-penetrating injury. The primary lesion was undiagnosed, and only late physical examination revealed a scapula alata with a deficiency in shoulder protrusion and elevation. Surgical exploration with direct suturing of the nerve was performed 2 months after the initial trauma; full restoration of muscle function was obtained 12 months after the surgical procedure. Pain, the dominant preoperative feature, totally disappeared after restoration of shoulder function. Although infrequent, spinal accessory nerve lesions must always be excluded in cases of penetrating injuries in the posterior triangle of the neck. Emphasis is placed on diagnosis and treatment of this condition.

The in vitro influence of eight hormones and growth factors on the proliferation of eight sarcoma cell lines.

Little is known about the regulation of sarcoma proliferation by hormones and/or growth factors. We therefore characterised the in vitro proliferative influence on eight sarcoma cell lines of the platelet-derived growth factor, the insulin-like growth factor 1, triiodothyronine, the epidermal growth factor, the luteinising-hormone-releasing hormone, progesterone, gastrin and 17 beta-oestradiol. The influence of the different factors on the proliferation of sarcoma cell lines was measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Two culture media were studied: (1) a nutritionally poor medium containing 2% of fetal calf serum and (2) a nutritionally rich one containing 5% or 10% FCS both with and without the addition of non-essential amino acids. The results were analysed either by conventional statistical analyses or by a classification method based on a decision-tree approach developed in Machine Learning. This latter method was also compared to other classifiers (such as logistic regression and k nearest neighbours) with respect to its accuracy of classification. Monovariate statistical analysis showed that each of the eight cell lines exhibited sensitivity to at least one factor, and each factor significantly modified the proliferation of five or six of the eight cell lines under study. Of these eight lines one of fibrosarcoma origin was the most "factor-sensitive". Decision-tree-related data analysis enabled the specific pattern of factor sensitivity to be characterised for the three histological types of cell line under study. The effects of hormone and growth factors are significantly influenced by the type of culture medium used. The method used appeared to be an accurate classifier for the kind of data analysed. Sarcoma proliferation can be modulated, at least in vitro, by various hormones and growth factors, and the proliferation of each histopathological type exhibited a distinct sensitivity to different hormone and/or growth-factors.

[Surgical closure of leg ulcers]. / Fermeture chirurgicale des ulcères de jambe.

Surgical closure of leg ulcers has to be preceded by treatment of their etiologies in order to avoid recurrences. Best coverage technique is achieved with the use of a meshed split thickness skin graft, harvested with a dermatoma. Skin graft take depends on the vascular quality of the recipient bed, on the technique used and also on the post-operative care.

[Pressure sores: management and treatment]. / Escarres: conduite à tenir et traitement.

The global management of pressure sores is best ensured with a multidisciplinary approach. We present the experience of the "Groupe de Travail Escarres" (Pressure Sore Workgroup) which gathers physicians and nurses interested with this pathology. The majority of the decubitus ulcers will heal spontaneously with a conservative treatment only. This treatment typically aims at relieving the causes that lead to pressure sores, at eliminating the necrotic tissues, at obtaining favourable local conditions to allow wound healing and at controlling the health status of the patient. Surgical treatment of pressure sores is indicated when wound healing does not occur and when the health status of the patient is sufficiently good. Defect coverage is best carried out using myocutaneous flaps since their excellent blood supply allows a good cleansing of the wound.

Contribution of quantitative lectin histochemistry to characterizing well-differentiated, dedifferentiated and poorly differentiated liposarcomas.

OBJECTIVE: To find new diagnostic markers in the group of lipomatous tumors. STUDY DESIGN: The histochemical lectin staining pattern was characterized in a series of 45 lipomatous lesions, including 10 typical lipomas, 6 atypical lipomas, 8 well-differentiated, 6 myxoid, 5 dedifferentiated and 10 pleomorphic liposarcomas. Three lectins were used-peanut (Arachis hypogaea) agglutinin, which binds to terminal Gal(beta 1,3)GalNAc residues; wheat germ (Triticum vulgare) agglutinin (s-WGA, the succinylated form of WGA), which binds to ((1-4)-D-GlcNAc)n and Neu5NAc residues; and jack bean (Concanavalia ensiformis) agglutinin which binds to alpha-D-Man and alpha-D-Glc residues. Histochemical staining was quantitatively measured by means of a cell image processor. RESULTS: In the case of certain carbohydrate residues, typical lipomas closely resemble atypical lipomas, which in turn closely resemble well-differentiated liposarcomas; typical lipomas differ significantly from well-differentiated liposarcomas. This indicates that atypical lipomas, or at least some of them, could represent a biologic link between typical lipomas and well-differentiated liposarcomas. While well-differentiated and pleomorphic liposarcomas differed significantly from each other, the poorly differentiated component of dedifferentiated liposarcomas included histochemical lectin properties, which were common to both well-differentiated and pleomorphic liposarcomas. CONCLUSION: Some atypical lipomas exhibit glycohistochemical characteristics that are common to those of well-differentiated liposarcoma. The poorly differentiated component of dedifferentiated liposarcomas remains more differentiated in terms of glycohistochemical markers than do poorly differentiated pleomorphic liposarcomas.

In vitro characterisation of soft tissue tumor chemosensitivity.

BACKGROUND: The benefit of performing chemotherapy on soft tissue sarcomas remains controversial. The present study deals with the in vitro characterisation of the influence of 3 antitumoral agents on the growth of 8 sarcoma cell lines. MATERIALS AND METHODS: Cell growth was monitored by means of the MTT colorimetric assay, which was further validated by a direct cell counting method. The three drugs tested included doxorubicin (ADR), cisplatin (DDP) and dacarbazine (DTIC). ADR was tested at 10(-5) M, 10(-6) M and 10(-7) M; DDP at 10(-5) M, 10(-6) M and 10(-7) M; and DTIC at 10(-3) M, 10(-4) M and 10(-5) M. A combination of the three drugs was also tested in order to ascertain whether a synergistic effect on cell growth inhibition could be obtained. A potential antineoplastic agent-induced influence on cell growth was determined 3 days after the addition of the diverse drug(s) to the culture media. The cell concentration was specifically adapted to each cell line. The 8 cell lines included 3 leiomyosarcomas, 1 malignant mixed Müllerian tumour, 3 rhabdomyosarcomas and 1 fibrosarcoma. RESULTS: The results show that of the three drugs tested, ADR was the most efficient in terms of the level of cell growth inhibition obtained and the number of cell lines whose growth was significantly inhibited. Of the three drugs, the least active was DDP. A significant synergistic effect was observed when the three drugs were added together to the culture medium. This synergistic effect was evident at the lowest doses tested for each drug. Whatever the histopathological type, the 8 cell lines exhibited a wide range of response to chemotherapy. CONCLUSIONS: The present study shows that the inhibition induced by 10(-7) M ADR, 10(-7) M DDP and 10(-5) M DTIC on sarcoma cell line growth is significantly more efficient than if each agent is tested individually. The in vitro methodology used here fits in with clinical reality because it enables sarcoma cell heterogeneity to be taken into account.