Limited value of routine microbiological diagnostics in patients hospitalized for community-acquired pneumonia

Current guidelines recommend microbiological diagnostic procedures as a part of the management of patients hospitalized for community-acquired pneumonia (CAP), but the value of such efforts has been questioned. Patients hospitalized for CAP were studied retrospectively, focusing on the use of aetiological diagnostic methods and their clinical impact. Adult patients, without known human immunodeficiency virus infection, admitted to hospital for CAP during 12 months, were evaluated with regard to the importance of aetiological diagnosis for tailoring antibiotic therapy, antibiotic-associated diarrhoea, Clostridium difficile disease, length of hospital stay and mortality. Of the 605 studied patients, 482 (80%) were subjected to Mycoplasma pneumoniae and/or respiratory virus serology and/or cultures of blood and/or sputum. They had a better prognosis than patients not subjected to microbiological diagnostics (mortality within 3 months was 9% vs 24%, p = 0.001), apparently reflecting differences in general health (e.g. less dementia diagnosis) but not the outcome of diagnostics. A presumptive aetiology was obtained only in 132 of the 482 patients, Streptococcus pneumoniae and M. pneumoniae being the most common agents (in 49 and 36 patients, respectively). Establishing an aetiological diagnosis had no impact on the number of in-hospital changes of therapy, on the proportion of new regimens having a narrower antimicrobial spectrum than the initial one or on the outcome. Therapy was changed to a drug directed specifically against the identified pathogen in only 16 out of these 132 patients and again without any overall improvement in the outcome variables. In a setting with a low frequency of antibiotic-resistant respiratory tract pathogens current routine microbiological diagnostics were found to be of limited value for the clinical management of patients hospitalized for CAP. Improved diagnostics in CAP are urgently needed, as establishing an aetiological diagnosis carries a potential for optimizing the antibiotic therapy.     

Challenges in midface reconstruction

Defects of the midface and maxilla are often the most challenging problems faced by the reconstructive surgeon. Resections that involve critical structures of the face such as the nose, eyelids, and lips in conjunction with the maxilla can be particularly difficult to reconstruct. The algorithm for reconstruction of these defects is usually based on the extent of maxilla that is resected. A classification system for maxillectomy defects is the most useful way to approach these reconstructions. A vast majority of extensive defects involving the maxilla and midface require free flap reconstructions. The type of flap selected is based on the extent of skin, soft tissue, and bone that is resected. Smaller volume defects with large skin surface requirements are best reconstructed with the radial forearm fasciocutaneous or osteocutaneous flaps. Larger soft-tissue volume and skin surface can be provided by the rectus abdominus myocutaneous flap. Critical structures such as lips, eyelids, and nose should be reconstructed separately, using local flaps if at all possible. The free tissue transfer should ideally not be incorporated into these structures. Most patients with even the largest resections can be restored to fairly good function by following this algorithm. Semin. Surg. Oncol. 19:218-225, 2000.     

Expression of T cell immunoglobulin- and mucin-domain-containing molecules-1 and -3 (TIM-1 and -3) in the rat nervous and immune systems

Expression of T cell immunoglobulin- and mucin-domain-containing molecules (TIMs) can be used as T helper (Th) differentiation markers in the human and mouse. We examined the expression of TIM-1 and -3 mRNAs in rat MBP(63-88)-induced experimental autoimmune encephalomyelitis (EAE). TIM-3 expression was upregulated in the spinal cord during EAE and following antigen restimulation of the encephalitogenic TCRBV8S2+ population. Interestingly, TIM-3 expression was also detected by in situ hybridization in resident cells of the nervous system. TIM-1 was expressed in B cells but not in resident CNS cells and TIM-1 mRNA levels in spinal cord were unchanged throughout the course of EAE. These results support the notion that TIM-3 can also be used as a Th1 differentiation marker in the rat. However, expression of TIM-1 and -3 is not restricted solely to T cells and the presence of TIM-3 in resident CNS cells may indicate a role for this molecule in the interaction between the nervous and immune systems.     

Tissue expansion after inverted-T mammaplasty: can it be performed successfully?

Breast cancer patients will occasionally need to undergo mastectomy after previous reduction mammaplasty or mastopexy. The presence of the "inverted-T" scar presents a unique reconstructive dilemma: Do mastectomy flaps that are traversed by surgical scars still allow for adequate tissue expansion and a good aesthetic result? The objective of this study was to evaluate the authors' experience with tissue expansion/implant reconstruction in patients with an inverted-T scar. All patients who underwent tissue expansion and implant reconstruction after inverted-T mammaplasty were reviewed retrospectively to determine aesthetic results, patient satisfaction, and complication rates associated with this reconstructive technique. During a 6-year period (1995-2001), 11 patients (12 breasts) underwent breast reconstruction with tissue expansion and implant placement after either reduction mammaplasty (N = 8) or mastopexy (N = 4). All patients reached target expansion volumes. After successful tissue expansion, exchange to either saline (N = 7) or silicone (N = 5) implants was performed. The mean follow-up period after implant exchange was 18.5 months (range, 2-72 months). Complications were minimal and included partial flap necrosis (N = 1). Aesthetic appearance and symmetry were judged to be good or excellent in the majority of patients. Overall patient satisfaction was high. Tissue expansion with implant exchange is an effective reconstructive technique for mastectomy defects after previous inverted-T mammaplasty. In this series, good to excellent aesthetic results were achieved in the majority of patients with minimal associated complications.     

Simplifying microvascular head and neck reconstruction: a rational approach to donor site selection

The purpose of this study was to review the authors' 13-year experience with free tissue transfer for head and neck oncology patients. This study was a retrospective review of 728 free flaps performed in 698 patients. Recipient sites were subdivided by region into the mandible (N = 253), mid face/orbit (N = 190), hypopharynx (N = 134), oral cavity (N = 104), skull base (N = 36), and scalp (N = 11). The overall free flap success rate was 98.6%. Seventy-nine flaps (10.9%) were reexplored for vascular compromise. Ten flaps (1.4%) were lost in their entirety. The overall complication rate was 17.5%. Four donor sites (forearm, fibula, rectus, and jejunum) were used for 92% of the patients. The results of the study confirm the efficacy of free tissue transfer in the reconstruction of oncological head and neck defects. In this series the free forearm, fibula, rectus, and jejunum flaps have become the workhorse donor sites for the vast majority of defects.     

Soft-Tissue reconstruction of the face using the folded/multiple skin island radial forearm free flap.

Resection of malignant soft-tissue tumors of the face often results in defects of skin, lining, and contour. When local tissues are unavailable, the folded/multiple skin island forearm free flap has been used to correct complex lining, skin, and contour defects concomitantly. This study is a retrospective review of all patients reconstructed with folded/multiple skin island forearm flaps from 1992 to 2000. Facial defects included facial skin, mucosal lining, and intervening soft tissue. Reconstruction was immediate and was not combined with another local flap. There were 17 patients (mean age, 61 years). Five patients had cutaneous malignancies and 12 patients had either mucosal or salivary gland malignancy. Defects were of the cheek and nose either alone or in combination. Defects ranged from 9 to 54 cm2. Nine patients had defects of either the skin or the mucosa with an associated soft-tissue component. These were reconstructed with a folded forearm flap with one skin island. Eight patients had full-thickness defects and were reconstructed with a folded flap with two skin islands. Flap survival was 100%. One case required reexploration for hematoma. Aesthetic results were good to excellent in 76% of patients. Delayed wound healing at the donor site occurred in 2 patients (11%). The folded/multiple skin island forearm flap is a useful tool for single-stage reconstruction of complex facial defects requiring replacement of skin, lining, and intervening soft tissue. Good to excellent aesthetic results can be expected in most patients.     

Nitric oxide stimulatory and endothelial protective effects of idoxifene, a selective estrogen receptor modulator, in the splanchnic artery of the ovariectomized rat

Estrogen is known to stimulate endothelial nitric oxide production and attenuate endothelial dysfunction after ischemia and reperfusion. However, estrogen therapy increases the risk of breast and endometrial cancer. The present study was designed to determine whether idoxifene, a selective estrogen receptor modulator without adverse effects on reproductive organs, may stimulate nitric oxide release and protect endothelial function. In U-46619 precontracted superior mesenteric arterial (SMA) segments isolated from ovariectomized rats, idoxifene and 17 beta-estradiol resulted in a comparable dose-dependent vasorelaxation (maximal relaxation: 75.3 +/- 4.9 and 71 +/- 4.7%, respectively). Treatment of the rings with N(omega)-nitro-L-arginine methyl ester completely blocked idoxifene- and 17 beta-estradiol-induced vasorelaxation. In vitro incubation of SMA rings with TNF alpha significantly reduced vasorelaxation to an endothelium-dependent vasodilator, acetylcholine (maximal relaxation: 73 +/- 3.7 versus 95 +/- 2.9% pre-TNF alpha, P <.01). Idoxifene, but surprisingly not 17 beta-estradiol, prevented TNF alpha-induced endothelial dysfunction (maximal relaxation: 86 +/- 2.6% in idoxifene-treated rings and 77 +/- 5.1% in 17beta-estrogen-treated rings). In vivo ischemia and reperfusion resulted in significant endothelial dysfunction as evidenced by decreased vasorelaxation to acetylcholine (maximal relaxation: 48 +/- 5.5 versus 92 +/- 3.9% in normal SMA rings), but a normal relaxation response to an endothelium-independent vasodilator, acidified NaNO(2) (95 +/- 3.2%). Treatment with idoxifene at either 1 or 2 mg/kg/day, or 17beta-estrogen at 1 mg/kg/day for 4 days significantly preserved endothelial function (P <.01 versus vehicle). Taken together, these results demonstrate that idoxifene is an endothelium-dependent vasodilator and exerts significant endothelial protective effects against TNF alpha- and ischemia-reperfusion-induced endothelial injury. These results suggest that selective estrogen receptor modulators have therapeutic potential in diseases where endothelial dysfunction plays an important role.     

Characterization of neuromedin U effects in canine smooth muscle

Two endogenous receptors for the potent smooth muscle-stimulating peptide neuromedin U (NmU) have recently been identified and cloned. Pharmacological, binding, and expression studies were conducted in an attempt to determine the receptor(s) involved in the smooth muscle-stimulating effects of NmU. The NmU peptides caused a concentration-dependent contraction of canine isolated urinary bladder. NmU did not have this same effect in the urinary bladder from rat, guinea pig, rabbit, mouse, or ferret. Although NmU had no effect on canine uterus it did cause contraction of canine stomach, ileum, and colon. As well as causing contraction of canine bladder in vitro, NmU administered systemically resulted in a significant increase in urinary bladder pressure in vivo. High-affinity binding sites for NmU were identified in canine bladder. The four NmU peptides porcine NmU-8, rat NmU-23, human NmU-25, and porcine NmU-25 displaced (125)I-NmU-25 binding with similar K(i) values (0.08-0.24 nM). A different binding profile was revealed in human embryonic kidney-293 cells transiently expressed with the canine NmU-2 receptor where porcine NmU-8 (K(i) = 147.06 nM) was much less potent than the other NmU peptides. Using TaqMan, expression of NmU-1 was detected in human urinary bladder, small intestine, colon, and uterus. Expression of NmU-2 was much lower or absent in these human tissues and undetectable in canine bladder and stomach. The results of this study reveal significant species differences in the activity of NmU. The contractile activity in human and canine smooth muscle seems to be mediated by the recently cloned NmU-1 receptor.     

Effect of adding exercise to a diet containing glucomannan

The aim of this study was to examine the effect of adding a total-body exercise program to an 8-week diet supplemented with glucomannan on weight loss, body composition, blood parameters, and physical performance in overweight men and women. Sedentary men and women who were overweight (body mass index>25 kg m(-2)) (men: 18-57 years, 27.0+/-11.2 years, 177.5+/-7.6 cm, 102.4+/-14.9 kg; women: 18-52 years, 33.4+/-12.1 years, 160.6+/-4.6 cm, 79.9+/-9.3 kg) completed an 8-week diet with 3000 mg glucomannan combined with either no exercise (No-Ex) (10 men, 10 women) or a resistance and endurance exercise training program (Ex) (12 men, 10 women). The diet emphasized healthy food choices and portion size control. The exercise training consisted of 3 weekly sessions of approximately 1 hour of a nonlinear periodized total-body resistance exercise program followed by 30 minutes of endurance exercise. After the intervention, there were reductions (P<.05) in body mass (men, -2.7+/-1.4 and -3.0+/-4.0 kg; women, -2.2+/-1.5 and -3.3+/-1.5 kg; No-Ex and Ex, respectively), fat mass (men, -2.3+/-1.6 and -3.9+/-2.5 kg; women, -2.6+/-1.4 and -3.6+/-1.1 kg; No-Ex and Ex, respectively), total cholesterol (TC) (men, -17.9+/-21.5 and -18.8+/-19.4 mg dL(-1); women, -9.3+/-20.0 and -10.1+/-19.5 mg dL(-1); No-Ex and Ex, respectively), and low-density lipoprotein cholesterol. Exercise significantly improved high-density lipoprotein cholesterol (HDL-C) (No-Ex, -2.0+/-4.7 and -2.3+/-4.5 mg dL(-1) vs Ex, 4.4+/-10.8 and 1.6+/-3.6 mg dL(-1); men and women, respectively), TC/HDL-C ratio, squat and bench press 1-repetition maximum, and distance covered during a shuttle-run test. In addition, exercise appeared to augment the reduction in fat mass (by 63% and 50%; men and women, respectively) and waist circumference, but did not affect total weight loss. Addition of a resistance and endurance exercise training program to a glucomannan diet regimen significantly improved measures of body composition, HDL-C, and TC/HDL-C ratio.