Different nutrient intake and prevalence of gastrointestinal comorbidities in women with endometriosis.

Even though endometriosis presents one of the most common gynaecological diseases, the pathogenesis is insufficiently studied. Besides immunologic, inflammatory or oxidative processes, recent studies also suggest an influence of nutrition on disease onset and progression. Because data about the actual nutrient intake of endometriosis patients are scarce, we aimed to examine the actual nutrient intake and potential influencing factors in these women. A total of 156 women with endometriosis (EM) and 52 age-matched controls were included in this retrospective case-control study. All women filled in a validated food frequency questionnaire to acquire the nutrient intake of the past 12 months and a disease-related questionnaire for the determination of disease status, clinical symptoms and comorbidities. Patients with endometriosis suffered significantly more from diet-related comorbidities like food intolerances (25.6% versus 7.7%; P = 0.009) and allergies (57% versus 31%; P < 0.001) compared to controls. Also gastrointestinal symptoms, including constipation, flatulence, pyrosis, diarrhea or frequent defecation, were higher in the EM group (77% versus 29%; P < 0.001). The nutrient intake of patients with endometriosis differed significantly compared to controls with a significantly lower ingestion of organic acids (P = 0.006), maltose (P = 0.0.16), glycogen (P = 0.035), tetradecenoic acid (P = 0.041), methionine (P = 0.046), lysine (P = 0.048), threonine (P = 0.046) and histidine (P = 0.049). The total intake of animal proteins was significantly lower in the EM group compared to the controls (P = 0.047). EM patients showed a decreased intake of vitamin C (P = 0.031), vitamin B12 (P = 0.008) and magnesium (P = 0.043) compared to controls. This study confirms a high association of endometriosis and gastrointestinal disorders accompanied by an altered nutrient intake. A dietary intervention by a professional nutritionist may help to reduce disease burden in the affected women.

Microbial patterns in patients with histamine intolerance.

Histamine intolerance represents a controversially discussed disorder. Besides an impaired degradation of orally supplied histamine due to diamine oxidase (DAO) deficiency, a deranged gut flora may also contribute to elevated histamine levels. Our aim was to determine the intestinal bacterial composition in patients with proven histamine intolerance in comparison to other food intolerances and healthy controls. A total of 64 participants were included in the study, encompassing 8 patients with histamine intolerance (HIT), 25 with food hypersensitivity (FH), 21 with food allergy and 10 healthy controls (HC). All participants underwent blood testing for total and food-specific immunoglobulin E, plasma histamine and DAO serum activity. Stool samples were used to analyze stool histamine and zonulin levels and bacterial composition by 16s rRNA sequencing. No significant differences in stool histamine levels were observed, but HIT patients showed elevated levels of stool zonulin. Microbiota analysis revealed increased levels of Proteobacteria (5.4%) and a significantly reduced alpha-diversity in the HIT group (P = 0.019). On family level, HC showed a significantly higher abundance of Bifidobacteriaceae compared to other study groups (P = 0.005), with lowest levels in the HIT group (P = 0.036). Also significantly reduced abundances of the genera Butyricimonas (P = 0.026) and Hespellia (P = 0.025) were observed in the HIT patients, whereas Roseburia were significantly elevated (P = 0.021). We concluded that the altered occurrence of Proteobacteria and Bifidobacteriaceae, reduced alpha-diversity as well as elevated stool zonulin levels suggest a dysbiosis and intestinal barrier dysfunction in histamine intolerant patients, which in turn may play an important role in driving disease pathogenesis.

Elucidating "lucidum": Distinguishing the diverse laccate Ganoderma species of the United States.

Ganoderma is a large, diverse and globally-distributed genus in the Basidiomycota that includes species causing a white rot form of wood decay on a variety of tree species. For the past century, many studies of Ganoderma in North America and other regions of the world have used the name G. lucidum sensu lato for any laccate (shiny or varnished) Ganoderma species growing on hardwood trees or substrates. Molecular studies have established that G. lucidum sensu stricto (Curtis) Karst is native to Europe and some parts of China. To determine the species of the laccate Ganoderma that are present in the United States, we studied over 500 collections from recently collected samples and herbarium specimens from hardwoods, conifers, and monocots. A multilocus phylogeny using ITS, tef1α, rpb1 and rpb2 revealed three well-supported clades, similar to previously reported findings. From the U.S. collections, thirteen taxa representing twelve species were identified, including: G. curtisii, G. lucidum sensu stricto, G. martinicense, G. oregonense, G. polychromum, G. ravenelii, G. sessile, G. tsugae, G. tuberculosum, G. cf. weberianum, G. zonatum, and Tomophagus colossus (syn. G. colossus). The species G. meredithiae is synonymized with G. curtisii, and considered a physiological variant that specializes in decay of pines. The designation G. curtisii f.sp. meredithiae forma specialis nov. is proposed. Species such as G. curtisii and G. sessile, once considered as G. lucidum sensu lato, were found to be divergent from one another, and highly divergent from G. lucidum sensu stricto. Morphological characteristics such as context tissue color and features (e.g. melanoid bands), basidiospore shape and size, geographic location, and host preference were found to aid in species identification. Surprisingly, G. lucidum sensu stricto was found in the U.S., but only in geographically restricted areas of northern Utah and California. These collections appear to have resulted from the introduction of this species into the United States possibly from mushroom growers producing G. lucidum outdoors. Overall, this study clarifies the chaotic taxonomy of the laccate Ganoderma in the United States, and will help to remove ambiguities from future studies focusing on the North American species of laccate Ganoderma.

Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls.

BACKGROUND: Histamine intolerance is thought to trigger manifold clinical symptoms after ingesting histamine-rich food due to reduced activity of diamine oxidase (DAO). No study has hitherto systematically assessed daily fluctuations of histamine levels and DAO activities in symptomatic patients. The aim of the study was to investigate the presence of histamine intolerance, to therefore establish day profiles of histamine levels and DAO activities, and to compare the results between patients with suspected histamine intolerance, food allergy and healthy controls. METHODS: We determined day profiles of histamine plasma levels and DAO serum activities in 33 patients with suspected histamine intolerance, in 21 patients with proven food allergy and in 10 healthy control patients. Clinical symptoms, food intolerances and further clinical and laboratory chemical parameters were evaluated. RESULTS: Twenty-four percent (8 of 33) suspected histamine-intolerant patients showed elevated histamine levels during the day. That might be caused by constantly and significantly reduced DAO activities in these patients compared to food-allergic and control patients. The remaining 25 patients presented normal histamine levels and DAO activities, but an increased prevalence of multiple food intolerances compared to the other subgroup of suspected histamine-intolerants. There was no correlation between subjective complaints and serological histamine parameters in patients with suspected histamine intolerance. CONCLUSIONS: We determined by daily profiling that decreased DAO activities correlated with elevated histamine levels in a subgroup of suspected histamine-intolerants. This finding discriminates these patients from food intolerant individuals with similar clinical symptoms and strongly suggests the presence of histamine intolerance.

Mistletoe therapy for human cancer: the role of the natural killer cells.

Extracts produced from Viscum album L. (mistletoe) as well as certain isolated components are able to stimulate different functions of the immune system. The natural killer cells have been suggested as one of the candidates for direct tumour cell destruction. These cells are defined by their ability to mediate non-major histocompatibility complex (MHC) restricted cytotoxicity without prior sensitization against a specific antigen. However, their effectiveness in tumor defence in vivo is unclear. In general, natural killer cells are unable to lyse fresh autologous tumour cells in vitro unless activated by interleukin-2-preincubation. The results of clinical studies are contradictory, but there is evidence that they may contribute to the prevention of the development of recidives and metastases. In this regard it is interesting that mistletoe extracts are able to stimulate natural killer cell-mediated cytotoxicity in vitro directly as well as indirectly in a cytokine-like manner, with the active components being carbohydrates rather than lectins. Clinical application of mistletoe extracts or isolated lectins is reported to induce augmentation of both number and activity of natural killer cells in peripheral blood in a dose-dependent manner; however, non-responders also have been described. In future work it has to be clarified whether a mistletoe-derived modulation of the natural killer system is of benefit in the tumour defence of cancer patients.

Effect of Viscum album L. on rapidly proliferating amniotic fluid cells. Sister chromatid exchange frequency and proliferation index.

Amniotic fluid cells (AFC) from 10 women undergoing amniocentesis were investigated. The 5-bromo-2'-deoxyuridine-induced sister chromatid exchange (SCE) frequency of AFC remained stable after the addition of a therapeutical concentration of Viscum album L. preparation Iscador P but decreased significantly after administration of high drug doses. As the proliferation index remained stable, even at extremely high drug concentrations, this effect could not be ascribed to a reduction of proliferation. No indications of cytogenetic damage or effects of mutagenicity were seen after the addition of Viscum album L. preparation P.

Bca77I: a new type-II restriction endonuclease from Bacillus caldolyticus cutting at the (A/T) increases CCGG(A/T) site.

We describe a new restriction enzyme recognizing a degenerate hexanucleotide sequence and cleaving the 5'-W increases CCGGW site (W = A or T). This enzyme cuts with high efficiency all four permutations of this sequence; ACCGGA (TCCGGT on the opposite strand), ACCGGT and TCCGGA. Methylation of the external cytosine completely blocks restriction while methylation of the internal cytosine only decreases the rate of restriction activity.

Bst71I: an isoschizomer of the type-IIS restriction enzyme, BbvI, recognizing the GCAGC(8/12) site.

A new type-IIS restriction enzyme, Bst71I, with the specificity 5'-GCAGC(N)8/3'-CGTCG(N)12 was isolated from Bacillus stearothermophilus (Promega No. 71). This enzyme is an isoschizomer of BbvI with somewhat improved characteristics for use by molecular biologists.

The use of pulsing electromagnetic fields to achieve arthrodesis of the knee following failed total knee arthroplasty. A preliminary report.

Treatment with pulsing electromagnetic fields was used as an adjunct in twenty patients who had had a knee arthrodesis after failure of a total joint arthroplasty. Eighteen had had an infected arthroplasty; one, mechanical loosening; and one, recurrent dislocation. Arthrodesis had been attempted twenty-five times in these twenty patients prior to application of the coils. These procedures included the use of twenty-two external fixation frames, one compression plate, one intramedullary rod, and one cylinder cast. Two groups of patients were identified: those with non-union and those with delayed union. Fourteen patients began treatment six months or more after arthrodesis and were considered to have a non-union. The other six patients started treatment less than six months after attempted arthrodesis because there was no evidence of progression toward union. They were considered to have delayed union. In seventeen (85 per cent) of the twenty patients a clinically solid arthrodesis with roentgenographic evidence of bone-bridging was achieved. The average time to union after coil therapy was started was 5.8 months, with a range of three to twelve months. The patients who started coil treatment earlier after arthrodesis showed a tendency to heal faster. The three patients who had failures were the only ones who did not adhere to the protocol, and all three were in the non-union group. All patients with a solid arthrodesis were free of pain and able to walk at the time of follow-up, nine to thirty-one months after the completion of treatment. The use of pulsing electromagnetic fields appears to be a valuable non-invasive adjunct when performing arthrodesis of the knee after failed total joint arthroplasty.

Treatment of therapeutically resistant non-unions with bone grafts and pulsing electromagnetic fields.

This study reviews the cases of eighty-three adults with ununited fractures who were treated concomitantly with bone-grafting and pulsed electromagnetic fields. An average of 1.5 years had elapsed since fracture and the use of this combined approach. Nearly one-third of the patients had a history of infection, and an average of 2.4 prior operations had failed to produce bone union. Thirty-eight patients who were initially treated with grafts and pulsed electromagnetic fields for ununited fractures with wide gaps, synovial pseudarthrosis, and malalignment achieved a rate of successful healing of 87 per cent. Forty-five patients who had initially been treated unsuccessfully with pulsing electromagnetic fields alone had bone-grafting and were re-treated with pulsing electromagnetic fields. Ninety-three per cent of these fractures healed. The residual failure rate after two therapeutic attempts, one of which was operative, was 1.5 per cent. The median time to union for both groups of patients was four months.

Congenital pseudoarthrosis of the tibia: treatment with pulsing electromagnetic fields.

Ninety-two patients with congenital pseudoarthrosis (infantile nonunion) were treated with pulsing electromagnetic fields (PEMF) in the United States and Europe in the past eight years. This represents the largest group of patients with infantile nonunions in which a common treatment modality has been used. Excluding the ten lesions (11%) which healed with refracture 48 lesions (59%) healed whereas 34 (41%) failed to heal. The success rate in 23 type I and 34 Type II lesions was 77% and 76%, respectively. Surgery in association with PEMF treatment did not improve the results of treatment. The most important variable was the radiographic morphology of the nonunion gap. Patients with spindled bone ends, a large gap and a grossly mobile lesion had a very poor prognosis relative to patients with a cystic or sclerotic transverse fracture line with a gap of less than 5 mm. The key to success in the treatment of infantile nonunions has been the combination of PEMF treatment with good orthopedic management, consisting of rigid immobilization, a nonweight-bearing status and rehabilitation with impact loading exercise. Infantile nonunion remains a major challenge to the orthopedic surgeon, but PEMFs appear to offer some important advantages for overcoming this pernicious condition. Dr. Harold Boyd's discussion of this paper follows. It was his final address to the AAOS.