Baseline Findings of PreventE4: A Double-Blind Placebo Controlled Clinical Trial Testing High Dose DHA in APOE4 Carriers before the Onset of Dementia.

INTRODUCTION: Lower blood levels of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) are correlated with worse cognitive functions, particularly among APOE ε4 carriers. Whether DHA supplementation in APOE ε4 carriers with limited DHA consumption and dementia risk factors can delay or slow down disease progression when started before the onset of clinical dementia is not known. METHODS: PreventE4 is a double-blind, single site, randomized, placebo-controlled trial in cognitively unimpaired individuals with limited omega-3 consumption and dementia risk factors (n=368). Its objectives are to determine (1) whether carrying the APOE ε4 allele is associated with lower delivery of DHA to the brain; and (2) whether high dose DHA supplementation affects brain imaging biomarkers of AD and cognitive function. RESULTS: 365 cognitively unimpaired individuals between 55 and 80 (mean age 66) were randomized to 2 grams of DHA per day or identically appearing placebo for a period of 2 years. Half the participants were asked to complete lumbar punctures at baseline and 6-month visits to obtain cerebrospinal fluid (CSF). The primary trial outcome measure is the change in CSF DHA to arachidonic acid ratio after 6 months of the intervention (n=181). Secondary trial outcomes include the change in functional and structural connectivity using resting state functional MRI at 24 months (n=365). Exploratory outcomes include the change in Repeatable Battery of the Assessment of Neuropsychological Status at 24 months (n=365). CONCLUSIONS: Findings from PreventE4 will clarify the brain delivery of DHA in individuals carrying the APOE ε4 allele with implications for dementia prevention strategies. Trial was registered as NCT03613844.

Standardization of radiograph readings during bowel management week.

INTRODUCTION: During "bowel management week," abdominal radiographs are used to monitor the amount and location of stool. A radiologist familiar with the treatment plan can provide an improved interpretation. The goal of this paper is to standardize the radiological reports during a bowel management week. METHODS: We saw 744 patients during bowel management week from May 2016 until March 2023. Diagnosis included: anorectal malformation (397), idiopathic constipation (180), Hirschsprung disease (89), and spina bifida (78). Laxatives were the treatment for 51% of patients, and 49% received enemas. Characteristic radiographs were selected for each treatment group for a proposed reading standardization. RESULTS: When the stool is visualized, it is crucial to report its location. Having a contrast enema helps with the correct interpretation of the colonic anatomy. It is also essential to always compare the amount of stool with the radiograph from the previous day to determine if there is an increase or decrease in stool. Examples of radiographs are shown to guide the use of the preferred proposed terminology. CONCLUSION: Providing information regarding which treatment modality the patient is receiving and stating that a patient is on a bowel management week treatment is crucial for the radiologist to provide adequate interpretation. The radiologist must be familiar with the treatment goals and purpose of the daily radiograph.

[Surgery and the zeitgeist: what happened to ethics and moral?]. / Chirurgie und Zeitgeist: Wo bleiben Ethik und Moral?

Ethical and moral topics have always been an integral part of surgery. The rapid progress of highly advanced medicine has induced public discussions about medico-ethical problems as well as respective legislation. Interdisciplinary ethical committees, appointed by political as well as professional associations, have published guidelines concerning current ethical topics. However, what about the doctor's attitude and the influence of the ever changing "Zeitgeist"? With the surplus of unproven health information on the web, modern information technologies have changed the doctor-patient relationship. Active leadership of the doctor is still required. For the benefit of the patient the physician should confront increasing economic pressures and the requirements of higher performance levels with competence. Indications have to be based on the results of valid quality controls. Special moral standards should be applied for working within the surgical community and for the pursuit of a career in academic surgery. By strengthening mutual respect and the community spirit surgery will remain attractive for aspiring young doctors.

Immune modulation by lactoferrin and curcumin in children with recurrent respiratory infections.

The clinical and immunologic effects of lactoferrin and curcumin (LC) oral supplementation were examined in healthy children with recurrent respiratory tract infections. Infections were reduced in children receiving LC. Immunologic analyses showed that LC supplementation resulted in a significant skewing of CD8+T lymphocytes maturation. Additionally: 1) CD14+, toll like receptor (TLR) 2-expressing cells augmented (p= 0.005) whereas CD14+/TLR4+ diminished (p= 0.004); and 2) IL10 production by CD14+ cells was reduced in children receiving LC. LC supplementation results in immune modulation and could be clinically beneficial.

[Allergic contact dermatitis to common ivy (Hedera helix L.)]. / Allergische Kontaktdermatitis auf Efeu (Hedera helix L.).

Common ivy (Hedera helix L.) is a ubiquitous plant in Europe whose major allergen falcarinol has moderate allergic potential. It is not related to poison ivy (Toxicodendron spp.). There are no cross reactions between the allergens of common ivy (falcarinol) and poison ivy (urushiol). Contact with common ivy or falcarinol may lead to sensitization and then a delayed hypersensitivity reaction. There are only few cases described in the literature. We report on a male hobby gardener with appropriate clinical history and positive patch test. The pathogenic mechanism is a type IV reaction following a sensitization exposure. Gardeners and landscape architects with frequent exposure to common ivy and thus a high risk of sensitization should wear appropriate protective clothing.

Gingko biloba (Rökan) therapy in tinnitus patients and measurable interactions between tinnitus and vestibular disturbances.

Tinnitus is one of the most important symptoms in neurootology after vertigo, nausea, and hearing loss. In most cases, the origin of the tinnitus remains inexplicable. Well-known, however, is that tinnitus may arise in any part of the hearing pathway (i.e., both within the cochlea receptor and in the temporal lobe and projections). Tinnitus also is associated frequently with vertigo, nausea and hearing loss. An age predominance exists, with tinnitus more common among those older than 40 years. From this starting point, a great demand exists today for new ideas and developments in the diagnosis and treatment of tinnitus.

Tenolysis and capsulectomy after hand fractures.

There are well established operative procedures for salvage of function after fracture healing. When hand therapy measures have not achieved a satisfactory range of motion, it is reasonable to remove any hardware, if present, and lyse tendon adhesions that prevent tendon gliding. The exact cause of restricted motion and the location of adhesions are not always predictable preoperatively, so the surgeon should anticipate additional procedures such as dorsal/palmar capsulectomies in combination with extensor and/or flexor tenolysis. The use of local anesthesia for direct patient input during the procedure offers great advantages. In the ideal situation there should be a demonstrable functional need in a compliant patient with a well healed fracture and workable articular surfaces. Competent hand therapy should be available postoperatively. The patient's main risk is worsening of the situation if surgery is unsuccessful. A marginal finger with poor neurovascular status may be better served by going to arthrodesis or even amputation. Tenolysis and capsulectomy, when indicated, are useful procedures in the salvage of these difficult problems.

Relationships between mesolimbic dopamine function and eating behavior.

These experiments are the first to correlate a specific stimulus of eating--the orosensory stimulation by sucrose--to mesolimbic dopaminergic activity. The pharmacological results and the increase in hypothalamic DOPAC/DA are convergent evidence for this relationship. The meaning of the relationship is not clear. The possibility that the decreased intake after dopaminergic receptor antagonist treatment and the increase in hypothalamic DOPAC/DA is related to the ingestive movements necessary for sham feeding seems unlikely for the following reasons: first, at least one dose of the antagonist had a preferential inhibition on sucrose intake compared to water intake; second, the D1 and D2 selective receptor antagonists decreased the initial rate of sucrose intake, but did not affect the rate of decay of sucrose intake over a 30-min test; third, in the second neurochemical experiment (Table 1), the volume ingested during 9 min of sham feeding 10% sucrose was not significantly different from the volume ingested from sham feeding 40% sucrose, but there was a significantly larger increase in the hypothalamic DOPAC/DA after 40% sucrose. Of course, a finer measurement of movements, such as lick rate, may reveal a significant difference that would correlate with the metabolic change. Fourth, striatal DOPAC/DA did not change during sham feeding of sucrose. Fifth, Bailey et al. demonstrated that a response-frequency summation analysis of the inhibitory effect of pimozide on sucrose intake did not reveal a motoric deficit. Thus, we interpret the increase of hypothalamic DOPAC/DA during the sham feeding of sucrose as evidence that activation of mesolimbic dopaminergic terminals in the hypothalamus is necessary for the normal processing of the central sensory and/or positive-reinforcing information produced by oral sucrose stimulation. Experiments are in progress to test this hypothesis and to attempt to distinguish between the sensory and positive-reinforcing effects of sucrose during sham feeding. In addition to generating this specific hypothesis concerning sucrose and hypothalamic DA activity, the results of these experiments suggest that the sham feeding preparation will be useful for the analysis of the important problem of the natural reinforcing properties of sweet taste. And finally, since sham feeding of sucrose is a form of oral self-stimulation, it provides a new experimental tool for comparing the role of central DA mechanisms in the positive-reinforcing effects of food, psychostimulant self-administration, and intracranial electrical self-stimulation.

[The risks of photochemotherapy (author's transl)]. / Die Risiken der Photochemotherapie.

The side effect of phototherapy with 8-methoxypsoralen was divided in short- and longterm damage. From 1969 till 1980 2 013 patients were treated. The pattern of alteration by PUVA depends on doses, continuance of therapy and type of dermatoses as psoriasis, vitiligo, mycosis fungoides, physical urticarias, chronic eczemas. The spontaneous development of tumors, the initiating or promotion of tumors by PUVA as well as a regression of tumors by PUVA has to be taken into account regarding the absolute numbers of tumors after PUVA-therapy. The risk of the PUVA-therapy depends on the doses of continuance of the treatment including the combination with other sources of radiations or natural sun-exposition. The possibilities of drug combinations to lower the total doses of light energy are discussed according the recommendation of several teams in Germany.

Renal calcium binding protein in the diabetic and vitamin D-depleted rat.

A calcium binding protein has been purified 220 fold from rat kidney. The molecular weight of this protein (26 000-28 000) is more than double that of the duodenal calcium binding protein of the rat. In response to the stimuli of both streptozotocin diabetes and depletion and repletion with vitamin D, changes in the renal protein are minimal. This contrasts markedly with responses of the duodenal protein to the same stimuli: (a) there was marked depression of duodenal calcium binding protein by vitamin D depletion and diabetes; (b) duodenal calcium binding protein was restored by vitamin D treatment of depleted rats. The renal protein appears to be identical with a previously described 28 000 molecular weight protein from the kidney purified by a different technique (Hermsdorf, C.L. and Bronner, F. (1975) Biochim. Biophys. Acta 379, 553-561). In contrast to findings of the current study, previous investigators were unable to isolate the protein from vitamin D-deficient rats and postulated vitamin D dependence. The protein activator of cyclic AMP phosphodiesterase is a calcium binding protein found in many tissues including kidney. Based on lack of response to stimuli we used and similarity in method of isolation and properties, our renal calcium binding protein may be this protein activator.

The effect of folic acid on gingival health.

On days 0 and 30 of a double blind study, two groups of 15 subjects each were evaluated using a plaque index, a gingival index, a gingival exudate flow and fasting plasma folic acid levels. Group I received 2 mg of folic acid twice daily for 30 days while Group II received a placebo. Results of the study seem to indicate that folic acid supplemented to the diet may increase the resistance of the gingiva to local irritants and thus lead to a reduction in inflammation.

Depressed duodenal calcium absorption in the diabetic rat: restoration by Solanum malacoxylon.

Duodenal calcium absorption is depressed in alloxan and streptozotocin diabetic rats taking normal amounts to dietary vitamin D. Depression of absorption appears to be at least in part the result of altered metabolism of vitamin D with failure to form 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), the vitamin D metabolite that acts directly on duodenum to stimulate calcium absorption. The South American plant Solanum malacoxylon causes extensive soft tissue calcification when ingested by cattle. An extract of this plant restores calcium absorption depressed by dietary strontium blockage of 1,25-(OH)2D3 formation in chicks. We gave an aqueous extract of S. malacoxylon to diabetic rats and restored duodenal calcium absorption to normal. These findings provide further evidence of the ability of a factor in the S. malacoxylon extract to mimic the actions of 1,25-(OH)2D3 on duodenal calcium transport and reinforce the hypothesis that abnormal vitamin D metabolism is an important determinant of depressed duodenal calcium absorption in diabetes.