Effect of Coenzyme Q10 Supplementation on Sarcopenia, Frailty, and Falls: A Scoping Review.

Coenzyme Q10 (CoQ10) is well-known for its antioxidant effects and has been highlighted in research related to aging and many age-related conditions. However, there is limited research on the benefit of CoQ10 supplementation in conditions impacting the physical robustness of older adults, such as sarcopenia, frailty, falls and osteoporosis. This scoping review identified and summarized 4 studies that assessed the effects of exogenous CoQ10 on outcomes relating to sarcopenia, frailty, and falls. Results of the studies showed statistically significant improvements in a variety of physical robustness related outcomes, however several limitations of these studies prevent conclusive recommendations from being drawn regarding the benefit of CoQ10 supplementation in these conditions. A well-designed randomized control trial assessing the benefit of CoQ10 supplementation on clinically relevant outcomes related to sarcopenia, frailty, and falls may be warranted.

Torsades de pointes - a report of a case induced by caesium taken as a complementary medicine, and the literature review.

WHAT IS KNOWN AND OBJECTIVE: Complementary medicines are commonly used by many patients. Caesium, a complementary therapy said to be of benefit for cancer treatment, has been associated with cardiac arrhythmias in the literature. We report a case of caesium-induced torsades de pointes and provide an evidence review. CASE SUMMARY: A 46-year-old woman with syncope experienced torsades de pointes and cardiac arrest. Upon admission her QTc was 620 ms. The patient had taken caesium carbonate 10 g daily for 1 month prior to admission. The patient was successfully resuscitated and discharged home after 35 days in hospital. WHAT IS NEW AND CONCLUSION: Ten cases of caesium-induced cardiac arrhythmias have previously been reported in the literature. Treatment strategies differed significantly among the cases. However, all patients recovered from the event. Complementary and alternative medicines should not be overlooked as a potential cause of serious adverse events.

Outcome of post-prostatectomy radiotherapy in one institution.

We present a retrospective study to evaluate the outcome of postoperative radiotherapy for biochemical or clinical recurrent prostate cancer. Twenty-six patients (median age 60 years) underwent radiotherapy after radical prostatectomy between January 1997 and January 2004. Seven patients received adjuvant radiotherapy and 19 received salvage radiotherapy. The median prostate-specific antigen at diagnosis was 8.6 (0.9-89) and most (23 patients) presented with T(3)N(0) disease. The median follow up was 19.5 months (5-84 months). All patients received a dose of 61.2 Gy at 1.8 Gy per fraction, 20 initially receiving 45 Gy to the lesser pelvis. The median dose to the bladder, rectum and left femoral head were 55.6, 57.5 and 33.8 Gy, respectively. All patients were managed radiotherapeutically by the first author. Twenty-four patients are alive. Two patients have died, one from oesophageal cancer and the second from metastatic prostate cancer. Two other patients also developed metastatic disease. Four asymptomatic patients with a rising prostate-specific antigen are under observation. None of the 26 patients has developed a local recurrence. Seven patients have developed grade 1 late bowel effects and three a grade 2 late effect. Eight patients suffer from grade 1 late genitourinary effects and two from grade 2 effects. One patient developed impotence, whereas 23 patients were rendered impotent postoperatively. There were no grade 3/4 late effects. Postoperative radiotherapy is well tolerated and provides effective local control.

Experiences with a compound method for estimating the time since death. I. Rectal temperature nomogram for time since death.

The temperature-based nomogram method for estimation of the time period since death was used at the scene of death as the primary method within a compound method in 72 consecutive cases. The situation and cooling conditions inspected and evaluated by the forensic pathologist at the scene are described as far as necessary to enable handling of the method. A comparison of the estimated period since death with the period determined by the police investigations demonstrates the reliability of the method. There were no contradictions in any of the 60 cases between the period of death estimated by this method and that determined by the police investigations. The criminal investigations were effectively supported in the earliest stages in 11 cases despite the fact that the period estimated was of considerable duration.

Experiences with a compound method for estimating the time since death. II. Integration of non-temperature-based methods.

The period since death was estimated at the scene in 72 consecutive cases using the temperature-based nomogram method as the primary method and supplemented by examination of criteria such as lividity, rigor mortis, mechanical and electrical excitability of skeletal muscle and chemical excitability of the iris. A case-oriented, computer-assisted selection of the non-temperature-based methods and integration of the results into a common result of the compound method was made following a special logistic. The limits of the period since death as estimated by the nomogram were improved in 49 cases by including the non-temperature-based methods and also provided results in 4 cases where the temperature method could not be used. In a further 6 cases the non-temperature-based methods confirmed the limits estimated by the temperature method but in 14 cases a useful result could not be obtained. In only one of the cases investigated was the upper limit of the period since death, as estimated by the criterion re-establishment of rigor (8 h post-mortem), in contradiction with the period determined by the police investigations (9.4 h post-mortem).

A tumor in the paracolpium. A case report.

A tumor in the paracolpium is very rare and generally only discovered by chance. In our patient, a leiomyoma was found. Only a few reports on this localisation have been published in the literature. Due to the variable clinical presentation of a leiomyoma of the vagina, it is difficult to differentiate between a malignant and a benign tumor. To discriminate between malignant and benign tumors, and to assess the surrounding structures, ultrasound, puncture and/or biopsy and CT-scan are the most common additional diagnostic techniques. However, in most cases, diagnosis is only made after histopathological examination. In our case report, the tumor was located in the upper part of the paracolpium and had no direct relation to the vagina. Surgical extirpation of the tumor was uneventful. Surgery is the recommended treatment.

A patient with interstitial deletion of the short arm of chromosome 3 (pter-->p21.2::p12-->qter) and a CHARGE-like phenotype.

We report on a 4-month-old boy with a de novo interstitial deletion of the short arm of chromosome 3 (pter-->p21.2::p12-->qter) and clinical findings typical of proximal 3p deletion together with coloboma of iris, heart defect, choanal atresia, retardation of growth and development, genital hypoplasia, and ear anomalies. Family history was unremarkable and parental chromosomes were normal. The clinical manifestations of the patient are compared with those of 10 patients previously described with a proximal 3p deletion. The additional CHARGE-like phenotype is discussed.

Initial community site development for first--and second-year medical students.

BACKGROUND: Many medical schools are planning community-based experiences for preclinical students. As part of a generalist physician initiative, the University of Texas Medical Branch in Galveston placed all 200 first-year medical students in generalists' offices in a new course, called the "Community Continuity Experience." METHODS: Driven by significant time, class size, and geographic constraints, a process managed by the local Area Health Education Center was formulated for identifying and developing potential sites. The final process included identification of candidate generalist sites, departmental participation, and a detailed site assessment. The individual office nurses were the focus of site development activities. RESULTS: Feedback indicated that having office nurses serve as site facilitators was effective, and a key enabling strategy was having a nurse site coordinator serve as a single point of contact for all the sites. The students expressed positive views of the site experience and an interest in assignment, rather than student choice, for site allocation. CONCLUSIONS: Important components of site development for such a new course are development of an accurate database of available generalist community faculty, a methodical site selection process, an early orientation for all involved, and consideration of nonphysician site facilitators during the start-up phase.

Hereditary multi-infarct dementia unlinked to chromosome 19q12 in a large Scottish pedigree: evidence of probable locus heterogeneity.

Hereditary multi-infarct dementia is a rare autosomal dominant disorder that predominantly affects the cerebral white matter. A locus was recently mapped in French pedigrees to chromosome 19q12. We have examined a large Scottish pedigree with neuropathologically confirmed hereditary multi-infarct dementia using polymorphic DNA markers spanning the 19q12 region and found no evidence of linkage. This suggests that, as in familial Alzheimer's disease, there is more than one locus.

Regulation of growth of LNCaP human prostate tumor cells by growth factors and steroid hormones.

The mitogenic activity of several growth factors on androgen responsive LNCaP human prostate tumor cells was studied. A two-fold stimulation of cell proliferation was observed after a culture period of 6 days in 1 ng EGF/ml, 10 ng TGF-alpha/ml or 20 ng basic FGF/ml. TGF-beta (0.02 ng/ml), which did not affect cell proliferation when added alone to the culture medium, inhibited the EGF- and TGF-alpha-induced growth. The synthetic androgen R1881 (0.1 nM) stimulated cell proliferation three-fold and increased the number of EGF receptors from 11500 to 28500 sites/cell. One of the mechanisms involved in androgen action on these cells is therefore an increased EGF receptor expression and increased sensitivity to EGF. TGF-beta did not directly affect androgen-responsive growth but inhibited the synergistic effect of EGF. A considerable expression of TGF alpha (precursors) could be demonstrated on the cells by immunohistochemical staining. However the staining intensity was not affected by androgens. These results make it less likely that androgen-responsive growth is mediated by regulation of secretion of an EGF- or TGF alpha-like activity, which in turn acts in an autocrine manner to stimulate growth. Estrogens, progestagens and antiandrogens do not inhibit androgen responsive growth of LNCaP cells but have striking growth stimulatory effects, increase EGF receptor level and increase acid phosphatase secretion. LNCaP cells contain a modified androgen receptor system with respect to both steroid specificity and antiandrogen sensitivity. It has recently been shown that the stimulatory effects are due to a mutated amino acid in the steroid binding domain of the androgen receptor.

The human prostatic cancer cell line LNCaP and its derived sublines: an in vitro model for the study of androgen sensitivity.

The LNCaP-FGC (fast growing colony) cell line, a subline derived from the LNCaP cell line, shares all the main characteristics, including its androgen sensitivity, described for the parental line. A number of sublines originating from the FGC line were characterized with respect to their response to steroid-depleted medium and to the synthetic androgen R1881. The growth of FGC cells in DCC medium with 0.1 nM R1881 was stimulated 2-3-fold compared to growth in DCC medium only. FGC cells that were continuously grown in DCC medium did not die, but their growth rate was clearly slowed down, and the cells remained responsive to androgen. These cells, therefore, have the androgen-sensitive, rather than the androgen-dependent phenotype. As cells of the subline FGC-JB could not be maintained in DCC medium, these cells better represent the androgen-dependent cell type. In contrast to the FGC line, cells of the R line, grew equally well in medium with complete or DCC serum. Under none of these culture conditions, R cells could significantly be stimulated further with R1881. Further analysis of the LNCaP-FGC sublines should provide valuable information concerning the development of androgen resistance in human prostate cancer.

Stimulatory effects of antiandrogens on LNCaP human prostate tumor cell growth, EGF-receptor level and acid phosphatase secretion.

LNCaP cells (derived from a lymph node carcinoma of the human prostate) show androgen responsive growth. Progestagens, estradiol and antiandrogens competed with androgens for binding to the androgen receptor in the cells to a higher extent than in other androgen-sensitive systems. Optimal growth (3-4 fold increase in DNA content of 6 day cell cultures vs controls) was observed after addition of the synthetic androgen R1881 (0.1 nM). Both steroidal and non-steroidal antiandrogens did not suppress the androgen responsive growth. At a concentration of 10 nM cyproterone acetate or 100 nM RU 23908, growth was even stimulated to an extent comparable to that observed after addition of androgen. Cyproterone acetate and RU 23908 also increased the number of epidermal growth factor receptors expressed at the cell surface to a comparable level as did the androgen. Like androgens, cyproterone acetate, RU 23908 or estradiol stimulated the secretion per cell of prostate specific acid phosphatase in the culture fluid. In conclusion, antiandrogens can exert striking stimulatory effects on the proliferation of LNCaP cells probably due to a defective androgen receptor system. It is discussed that comparable changes in the specificity of the androgen receptor in prostate cancer cells may give these cells an advantage in growth rate and may contribute to development of tumors characterized as hormone independent.

Antiproliferative effects of suramin on androgen responsive tumour cells.

UNLABELLED: The effect of the polyanionic drug suramin on two androgen responsive tumour cell lines was studied. Human prostate tumour (LNCaP) cell growth is stimulated two- to three-fold by the synthetic androgen R1881 (0.1 nM) or EGF (1 ng/ml). Suramin (0.01-1.0 mM) inhibited the growth of LNCaP cells in a dose dependent way, both in the presence and absence of androgen or EGF. Growth was arrested in the G0/G1 phase of the cell cycle, but was resumed after removal of suramin. DDT-1 hamster ductus deferens tumour cells are stimulated by PDGF (25 ng/ml), b-FGF (10 ng/ml) and testosterone (10 nM). Suramin inhibited PDGF and b-FGF stimulated cell growth. However in the presence of testosterone, suramin showed a biphasic effect: stimulatory at low dose (0.01 mM) and inhibitory above 0.01 mM. Suramin decreased the apparent affinity of EGF binding sites on LNCaP cells with a two- to eight-fold increase in Kd at 0.1 and 1.0 mM suramin, respectively. IN CONCLUSION: suramin counteracts the growth stimulatory effects of both androgens and growth factors on androgen sensitive tumour cells. The effects are reversible after withdrawal of suramin.

[Sudden death in urticaria pigmentosa]. / Plötzlicher Tod bei Urticaria pigmentosa.

A case of sudden death of a 25-year-old man, with a six years history of Urticaria pigmentosa, is reported. On a cold morning in November he was found lying dead on the lawn. Histology revealed no signs of systemic mastocytosis. The biochemical investigations (high free histamine level in urine) in addition to a BAC of 0,72 mg/g and the scene conditions (cold irritation) explained the mechanism of death, a systemic anaphylactoid reaction.

[Diurnal differences in alcohol absorption]. / Tageszeitliche Unterschiede der Alkoholresorption.

Under standardized conditions five subjects were submitted twice to a dose of alcohol of 1.1 g/kg. This dose was administered once between 7:15 and 7:45 am. and at a different day between 7:15 and 7:45 pm. The blood alcohol concentration curves in the morning and the evening differed significantly in peak and time elapsed until this value was reached. During the morning the peak averaged 32% higher than in the evening. In the morning it was reached after about 60 min and during evening after 110 min. The elimination rate was about the same. These results show that alcohol is significantly faster absorbed into the blood in the morning than during the evening. This could be explained by accelerated transport of uptaken alcohol into the bowels.

Spinal cord degeneration associated with type II decompression sickness: case report.

The medical history, clinical and neuropathological findings at necropsy are described in a 50-year-old male amateur diver who suffered from Type II decompression sickness, a spinal 'bend'. He survived as a paraplegic for 4 years. In the spinal cord upward Wallerian degeneration in the posterior columns and downward degeneration in the corticospinal tracts was explained by multiple small and medium sized infarcts affecting the centripetal blood supply to the cord. There was preservation of a rim of subpial fibres on the surface of the posterior and lateral columns. The grey matter and nearby white matter (supplied by the centrifugal arterial supply) was unaffected.

Mechanism of androgen action: recent observations on the domain structure of androgen receptors and the induction of EGF-receptors by androgens in prostate tumor cells.

In this paper two different aspects of androgen action are reviewed. Polyacrylamide gel electrophoresis of androgen receptors, photoaffinity labeled with R1881 showed that receptors isolated from both human prostate cells and calf uterine cytosol cells are proteins with a molecular mass of approx 110 kD. Purification to homogeneity of this form of the receptor from calf uterus also yielded a 110 kD protein. A molecular model for the DNA-binding form of the receptor is presented in which one polypeptide comprises three active domains: one for ligand binding, one for interaction with nuclear acceptor sites, and a third domain which modulates nuclear interaction. Mild digestion with chymotrypsin or a protease from rat prostates removes the modulating domain and leaves the ligand binding and nuclear interaction domain intact. Trypsin treatment yields a fragment of lower molecular mass containing the ligand binding domain with some affinity for RNA, but not DNA. In vitro studies with a human prostate tumor cell line (LNCaP), suggest that androgens not only directly effect cell growth, but also act indirectly. Both epidermal growth factor (EGF) and androgens stimulate cell growth. In addition androgens stimulate synthesis of receptors for EGF. Thus androgens effect tumor cell growth by autocrine or paracrine mechanisms by making the cells more sensitive for growth factor mediated stimuli.