Topical ampicillin in the appendicectomy wound: Report of double-blind trial

One hundred and thirty unselected patients undergoing appendicectomy were treated with topical ampicillin powder or topical placebo powder (lactose) before closing the wound. The postoperative wound infection rates were 3% in the ampicillin-treated group and 24% in the control group, a significant difference. This difference was not influenced by the degree of inflammation in the appendix. No side-effects of treatment were observed.     

Oral nutritional supplementation accelerates skin wound healing: a randomized, placebo-controlled, double-arm, crossover study

Nutritional therapy is critical for wound healing in people with severe malnutrition or specific metabolic deficiencies. Medical claims from manufacturers of many oral supplements are marketed to surgical patients for decreasing edema, bruising, and discomfort. The effect of supplementing nutrients on soft-tissue wound healing in otherwise normal, healthy adults is an area of clinical importance, but little information is available. Proteolytic enzymes have been reported to moderate the inflammatory cycle and may up-regulate the healing process. The goal of this study was to perform a clinical trial in normal, healthy adults that examined the effects of an oral nutritional supplement (InflammEnz, Enzymes, Inc., Parkville, Mo.) on soft-tissue healing times. Twenty-six normal, healthy volunteers were recruited into a randomized, crossover, placebo-controlled, clinical trial consisting of two phases, each lasting 21 days. In phase I, subjects were subjected to a 3-mm forearm skin biopsy and randomly received a placebo or oral supplement (four capsules per day for 7 days). After a 2-week washout period, a second biopsy was performed to start phase II, with each subject receiving the respective placebo or supplement capsules. Digital photographs were taken during wound healing in both phases and analyzed for wound areas (in square millimeters) and perimeters (in millimeters). Twenty-two subjects completed the clinical trial. On the basis of wound surface areas, 17 subjects had improved wound healing and five subjects did not respond or responded only slightly to the supplement treatment. The mean +/- SD healing time of the subjects responding to supplement-treated wounds was 15 +/- 2.2 days, compared with 18 +/- 2.5 days for the placebo group. The 17 percent acceleration of wound-healing time was significant (p < 0.005). In subjects responding to oral supplements, less redness in the wounds was observed that may have been associated with less inflammation. The authors' results demonstrate that InflammEnz oral supplementation accelerated soft-tissue wound healing in 77 percent of normal, healthy subjects studied. The authors' study validates observations made that this supplement modulates the wound-healing process and suggests that many patients with minor soft-tissue wounds may benefit from treatment.     

Placenta mesenchymal stem cell accelerates wound healing by enhancing angiogenesis in diabetic Goto-Kakizaki (GK) rats

Multipotent mesenchymal stem cells have recently emerged as an attractive cell type for the treatment of diabetes-associated wounds. The purpose of this study was to examine the potential biological function of human placenta-derived mesenchymal stem cells (PMSCs) in wound healing in diabetic Goto-Kakizaki (GK) rats. PMSCs were isolated from human placenta tissue and characterized by flow cytometry. A full-thickness circular excisional wound was created on the dorsum of each rat. Red fluorescent CM-DiI-labeled PMSCs were injected intradermally around the wound in the treatment group. After complete wound healing, full-thickness skin samples were taken from the wound sites for histological evaluation of the volume and density of vessels. Our data showed that the extent of wound closure was significantly enhanced in the PMSCs group compared with the no-graft controls. Microvessel density in wound bed biopsy sites was significantly higher in the PMSCs group compared with the no-graft controls. Most surprisingly, immunohistochemical studies confirmed that transplanted PMSCs localized to the wound tissue and were incorporated into recipient vasculature with improved angiogenesis. Notably, PMSCs secreted comparable amounts of proangiogenic molecules, such as VEGF, HGF, bFGF, TGF-β and IGF-1 at bioactive levels. This study demonstrated that PMSCs improved the wound healing rate in diabetic rats. It is speculated that this effect can be attributed to the PMSCs engraftment resulting in vascular regeneration via direct de novo differentiation and paracrine mechanisms. Thus, placenta-derived mesenchymal stem cells are implicated as a potential angiogenesis cell therapy for repair-resistant chronic wounds in diabetic patients.     

Treatment of subclinical hypothyroidism reduces atherogenic lipid levels in a placebo-controlled double-blind clinical trial.

Many studies have found clinical and metabolic alterations in subclinical hypothyroidism, however, there are disagreements about the benefits of levothyroxine therapy. The objective of the present study was to analyze the effects of 6 months of treatment on the lipid profile of patients with subclinical hypothyroidism. A randomized double blind, placebo-controlled clinical assay was conducted. Sixty patients were enrolled in stratified random allocation by TSH levels that generated similar groups in average: free thyroxine levels, lipid levels, age, clinical score, and sedentary. At 6 months, 18 patients in the levothyroxine and 20 in the placebo group were reevaluated and a fall in all atherogenic lipid variables was observed with treatment. The TC and LDL-c variations (-22.6+/-37.2 and -18.5+/-34.6 mg/dl, respectively) in the group that received LT4 were statistically different (p=0.023 and p=0.012) from those occurring in the placebo group (+7.3+/-37.1 and +14.7+/-40.6 mg/dl). Baseline characteristics associated with better improvement in the levels of TC and LDL-c were the presence of TPO-Ab, TSH levels >8.0 microUI/ml, Body Mass Index >or=25 kg/m2, and the presence of menopause. We concluded that treatment with dose-adjusted levothyroxine reduced atherogenic lipid levels in some patients. Further studies to determine the effects of LT4 replacement in specific subgroups of SH patients are still necessary, especially in patients with TSH <8.0 microUI/ml.     

Oral intake of Lactobacillus pentosus strain b240 accelerates salivary immunoglobulin A secretion in the elderly: A randomized, placebo-controlled, double-blind trial

Background

Immunoglobulin A (IgA) secretion in saliva decreases with age and may be the cause of increased vulnerability of the elderly to respiratory infections. The effect of oral intake of lactic acid bacteria on salivary secretory IgA (SIgA) in the elderly has not been reported. The objective of this study was to demonstrate the acceleration of salivary SIgA secretion by oral intake of Lactobacillus pentosus strain b240 (b240) in the elderly.

Results

A total of 80 healthy elderly individuals were randomly allocated to either an intervention (i.e., b240) or a control (i.e., placebo) group. The elderly individuals in the b240 group were given a sterile water beverage (125 mL) containing heat-killed b240 (4 × 10⁹ cells), while those in the placebo group were given only a sterile water beverage (125 mL); both groups received their respective beverages once daily for 12 weeks. Saliva was collected before initiation of the study and every 2 weeks thereafter. Saliva flow rate and SIgA concentration were determined, and the SIgA secretion rate was calculated. The mean salivary SIgA secretion rate in the b240 group steadily increased until week 4 (exhibiting a 20% elevation relative to that at week 0), and then remained stable until week 12. Changes in SIgA secretion rate over the intervention period were significantly greater in the b240 group than in the placebo group. The treatment groups exhibited no significant differences in adverse events.

Conclusions

Oral intake of L. pentosus strain b240 for 12 weeks significantly accelerated salivary SIgA secretion, thereby indicating its potential utility in the improvement of mucosal immunity and resistance against infection in the elderly.     

Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial.

Alpha-lipoic acid (ALA), a naturally occuring compound and a radical scavenger was shown to enhance glucose transport and utilization in different experimental and animal models. Clinical studies described an increase of insulin sensitivity after acute and short-term (10 d) parenteral administration of ALA. The effects of a 4-week oral treatment with alpha-lipoic acid were evaluated in a placebo-controlled, multicenter pilot study to determine see whether oral treatment also improves insulin sensitivity. Seventy-four patients with type-2 diabetes were randomized to either placebo (n = 19); or active treatment in various doses of 600 mg once daily (n = 19), twice daily (1200 mg; n = 18), or thrice daily (1800 mg; n = 18) alpha-lipoic acid. An isoglycemic glucose-clamp was done on days 0 (pre) and 29 (post). In this explorative study, analysis was done according to the number of subjects showing an improvement of insulin sensitivity after treatment. Furthermore, the effects of active vs. placebo treatment on insulin sensitivity was compared. All four groups were comparable and had a similar degree of hyperglycemia and insulin sensitivity at baseline. When compared to placebo, significantly more subjects had an increase in insulin-stimulated glucose disposal (MCR) after ALA treatment in each group. As there was no dose effect seen in the three different alpha-lipoic acid groups, all subjects receiving ALA were combined in the "active" group and then compared to placebo. This revealed significantly different changes in MCR after treatment (+27% vs. placebo; p < .01). This placebo-controlled explorative study confirms previous observations of an increase of insulin sensitivity in type-2 diabetes after acute and chronic intravenous administration of ALA. The results suggest that oral administration of alpha-lipoic acid can improve insulin sensitivity in patients with type-2 diabetes. The encouraging findings of this pilot trial need to be substantiated by further investigations.     

Oral premedication for operations on the face under local anesthesia: a placebo-controlled double-blind trial.

Modern strategies for preventing or controlling pain and anxiety demand a premedication for operations using local anesthesia and for those using sedation or general anesthesia. For optimal patient care, the premedication should be given orally and, with respect to the outpatient basis of the operations, should have a short recovery period. Midazolam, one of the most favored premedications for general anesthesia, has been recommended as a premedication for operations using local anesthesia as well. However, midazolam has only sedative-anxiolytic effects and does not reduce pain sensation, which should be mandatory for operations using local anesthesia. A further requirement is the maintenance of stable hemodynamics for the prevention of postoperative hematomas, especially in the face. For these reasons, another premedication meeting all requirements (anxiolysis, analgesia, and stable hemodynamics) was researched. A randomized, double-blind prospective study was performed from March of 1997 to June of 1998. Five groups totalling 150 patients were included in the study; each group contained 30 patients who had operations performed solely on the face. In the first four groups, the effect of midazolam (0.15 mg/kg(-1)), morphine (0.3 mg/kg(-1)), and clonidine (1.5 microg/kg(-1)) administered orally was compared with a placebo. The fifth group was the control group and received no premedication. To evaluate the effects of the premedications, a corresponding questionnaire was completed independently by the patient and surgeon. With regard to the anxiolytic or analgesic properties of the premedication, 61 percent of the patients preferred pain reduction to anxiety control, and 24 percent of patients preferred reduction of anxiety. The remainder insisted on a reduction of both properties (8 percent) or had no preference (7 percent). Reduction of anxiety was largest in the midazolam and the clonidine groups, but the difference was not significant. The least pain during the application of local anesthesia was experienced by the morphine group (37 percent) and the clonidine group (33 percent), in contrast to the midazolam group (60 percent) (p = 0.04). Morphine and clonidine met the requirements of pain reduction equally well. Nevertheless, considering the rate and intensity of adverse effects with respect to hemodynamic compromises, nausea, and emesis, clonidine is even better suited as an oral premedication for operations on the face using local anesthesia.     

Suppression of DNA damage in human peripheral blood lymphocytes by a juice concentrate: a randomized, double-blind, placebo-controlled trial

Chronic inflammation contributes to many prevalent diseases worldwide, and it is widely accepted that inflammatory molecules contribute to DNA damage. In this ancillary study, we investigated the influence of an encapsulated fruit and vegetable juice powder concentrate on peripheral blood lymphocytes (PBL) DNA damage. Using a double-blind, placebo-controlled approach, subjects were randomly assigned capsules containing placebo, or one of two formulations of the juice powder. Blood was drawn at baseline and after 60 days of capsule consumption. We found DNA damage in isolated PBL is suppressed after consumption of the encapsulated juice powder, and damage was correlated with the level of systemic inflammation. These data suggest a potential health benefit by consuming the juice concentrate capsules through their ability to suppress DNA damage as measured in surrogate tissues (PBL).     

A randomized,double-blind,placebo-controlled,clinical trial on probiotic soy milk and soy milk: effects on epigenetics and oxidative stress in patients with type II diabetes

This clinical trial aimed to discover the effects of probiotic soy milk and soy milk on MLH1 and MSH2 promoter methylation, and oxidative stress among type II diabetic patients. Forty patients with type II diabetes mellitus aged 35–68 years were assigned to two groups in this randomized, double-blind, controlled clinical trial. Patients in the intervention group consumed 200 ml/day of probiotic soy milk containing Lactobacillus plantarum A7, while those in the control group consumed 200 ml/d of conventional soy milk for 8 weeks. Fasting blood samples, anthropometric measurements, and 24-h dietary recalls were collected at the baseline and at the end of the study, respectively. Probiotic soy milk significantly decreased promoter methylation in proximal and distal MLH1 promoter region (P < 0.01 and P < 0.0001, respectively) compared with the baseline values, while plasma concentration of 8-hydroxy-2′-deoxyguanosine (8-OHdG) decreased significantly compared with soy milk (P < 0.05). In addition, a significant increase in superoxide dismutase (SOD) activity was observed in probiotic soy milk group compared with baseline value (P < 0.01). There were no significant changes from baseline in the promoter methylation of MSH2 within either group (P > 0.05). The consumption of probiotic soy milk improved antioxidant status in type II diabetic patients and may decrease promoter methylation among these patients, indicating that probiotic soy milk is a promising agent for diabetes management.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-015-0503-1) contains supplementary material, which is available to authorized users.     

Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial

Glutathione (GSH) dysregulation at the gene, protein, and functional levels has been observed in schizophrenia patients. Together with disease-like anomalies in GSH deficit experimental models, it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization, and thus possibly causing schizophrenia symptoms. To determine whether increased GSH levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients in a randomized, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). We analyzed whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs that were recorded at the onset, at the point of crossover, and at the end of the protocol. In this proof of concept study, the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes were robust both at the group and at the individual level. Although MPS increase was observed in the absence of clinical improvement at a group level, it correlated with individual change estimated by Liddle's disorganization scale. Therefore, significant changes in EEG synchronization induced by NAC administration may precede clinically detectable improvement, highlighting its possible utility as a biomarker of treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01506765.     

The influence of permanent magnetic field therapy on wound healing in suction lipectomy patients: a double-blind study

The authors present their experience with the healing influence of permanent magnets on postoperative wounds. The responses of 20 patients who underwent suction lipectomy and postoperative negative magnetic field therapy were studied in a double-blind fashion. Magnets in the form of patches (10 patients) or sham magnet patches (10 patients) were placed over the operative region in each of the patients. Pain, edema, and discoloration (ecchymosis) were evaluated at 1, 2, 3, 4, 7, and 14 days postoperatively. Our results show that the treatment group had significant reductions in pain on postoperative days 1 through 7, in edema on days 1 through 4, and in discoloration on days 1 through 3 when compared with the control group. These results demonstrated that commercially available magnets have a positive influence on the postoperative healing process in suction lipectomy patients.