The effect of limb position on the reliability of leg circumference measurements in patients diagnosed with lower limb lymphoedema.

OBJECTIVE: To establish the intrarater reliability of lower limb circumference measures in a sample of individuals who are diagnosed with lower limb lymphoedema and to evaluate if change in limb position has an effect on the reliability of circumferential measures. METHOD: A sample of forty-one adults diagnosed with a lower limb lymphoedema were recruited. Participants had their affected leg measured three times by a qualified therapist during a standard outpatient appointment: twice in a lying position and once in sitting with knee flexed at 90°. To examine the intrarater reliability, interclass correlation coefficients (ICC) with 95% confident intervals were calculated. RESULTS: Excellent intrarater reliability was established at each measurement point and for the sum of circumferential measures when the limb remeasured in the same position by the same therapist. Changing the position of the limb resulted in lower intrarater reliability values at 10 and 30 cm from the base of the foot. CONCLUSIONS: The current study provides evidence for the intrarater reliability of lower limb circumference measures and highlights the need for consistency when remeasuring and monitoring the limb of those diagnosed with lower limb lymphoedema. IMPLICATIONS FOR CANCER SURVIVORS: Lymphoedema is a significant problem for breast cancer survivors but also provides lifetime risk to all survivors of lymph node surgery for solid tumours. The monitoring and surveillance of leg circumference measures of people diagnosed with lower limb lymphoedema has been a valuable instrument when reviewing progress of this chronic condition.

COVID-19-Associated Bifacial Weakness with Paresthesia Subtype of Guillain-Barré Syndrome.

We report a case of bifacial weakness with paresthesia, a recognized Guillain-Barré syndrome subtype characterized by rapidly progressive facial weakness and paresthesia without ataxia or other cranial neuropathies, which was temporally associated with antecedent coronavirus 2019 (COVID-19). This case highlights a potentially novel but critically important neurologic association of the COVID-19 disease process. Herein, we detail the clinicoradiologic work-up and diagnosis, clinical course, and multidisciplinary medical management of this patient with COVID-19. This case is illustrative of the increasingly recognized but potentially underreported neurologic manifestations of COVID-19, which must be considered and further investigated in this pandemic disease.

Quality of life in breast cancer patients during chemotherapy and concurrent therapy with a mistletoe extract.

BACKGROUND: The effects of standardized aqueous mistletoe extracts on Health Related Quality of Life (HRQoL) of tumor patients needs further evaluation. METHODS: in this non-interventional, prospective clinical investigation the longitudinal course of Quality of Life of 270 breast cancer patients during adjuvant chemotherapy and mistletoe therapy with abnobaVISCUM(®) Mali was investigated. HRQoL was measured 4 times by self-assessment with the QLQ-C30 and QLQ-BR23 questionnaire of the European Organization for Research and Treatment of Cancer (EORTC): at the beginning of mistletoe- and chemotherapy, 4 weeks later, at the end of the chemotherapy and 4 weeks after finishing chemotherapy. Secondary objectives were the tolerability and safety of mistletoe therapy in combination with chemotherapy under conditions of daily practice. RESULTS: after an initial deterioration the average range of all obtained QLQ-C30 function scales (n=262, 48.9-71.5) remained stable even at the last chemotherapy cycle and improved significantly (p<0.0001) to 66.9-80.7 4 weeks later, compared to the initial visit. Also the QLQ-BR23 function scales significantly improved (p<0.0001) 4 weeks later. The symptom scales of the QLQ-C30 remained stable under chemotherapy even at the final chemotherapy cycle and decreased from 16.2 to 44.1 at the initial visit to 11.2-29.9 (p<0.001) at the final visit. These results were comparable to the subgroup with initial visit before chemotherapy (n=114) in which rather stable function scales during chemotherapy (difference of the mean values: 9.6 to -3.7) and only little increase of symptoms (difference: 13.2 to -4.9) was measured. The tolerability of the therapy was judged by the physicians as good or very good for 91% of the patients and the efficacy was rated as good or very good for 94%. 89% of the patients reported about a good or very good benefit. CONCLUSION: the overall results point to a relevant stabilisation of Health Related Quality of Life during various chemotherapy regimes, possibly due to a reduction of chemotherapy caused side effects with an excellent tolerability of the mistletoe therapy.

Anticancer activity of a lectin-rich mistletoe extract injected intratumorally into human pancreatic cancer xenografts.

BACKGROUND: In single case observations, tumour remissions after intratumoral injections of mistletoe extracts have been described. MATERIALS AND METHODS: We investigated the antitumour activity of intratumorally (i.t.)-injected lectin-rich mistletoe extract at different dosages and i.t.-injected mistletoe lectin I in comparison to intravenous (i.v.) Gemcitabine and i.t. treatment with placebo in a human pancreatic cancer xenograft. RESULTS: In a preliminary dose-response experiment, the most marked tumour inhibition was induced when mistletoe extract was given at 8 mg/kg body weight (BW) and mistletoe lectin I at 5.3 microg/kg BW. In a second experiment, bi-weekly i.t. injections of mistletoe extract over 8 weeks resulted in a very high antitumour activity with an optimal T/C value (=median relative tumour volume of the test group vs. the control) of 0.4% combined with 3/8 partial and 3/8 complete remissions. Gemcitabine was less active with 2/8 partial and 1/8 complete remissions and an optimal TIC of 4.6%. CONCLUSION: I.t.-injected lectin-rich mistletoe extract should be further evaluated in patients with inoperable locally advanced pancreatic cancer.

The feasibility of measuring three-dimensional facial morphology in children.

OBJECTIVE: An investigation to determine the feasibility of measuring soft tissue morphology in children using a three-dimensional laser-scanning device. DESIGN: Prospective clinical trial. SETTING AND SAMPLE POPULATION: University of Wales, College of Medicine and one secondary school in the South Wales region. Sixty live subjects (30 adults, 30 children) were recruited in the study. EXPERIMENTAL VARIABLES: Laser scanned images of the subjects were obtained under a reproducible and controlled environment with two Minolta Vivid 900 (Osaka, Japan) optical laser-scanning devices assembled as a stereo-pair. A set of left and right scanned images was taken for each subject and each scan took an average of 2.5 s. These scanned images were processed and merged to form a composite three-dimensional soft tissue reproduction of the subjects using commercially available reverse modelling software. OUTCOME MEASURE: The shell deviations between left and right scan of each patient were recorded and analysed for differences. These differences determined whether the subjects could remain still during the time of the scans. RESULTS: The results showed that the mean differences between shell deviations for the adult scans and children scans were 0.25 +/- 0.09 and 0.30 +/- 0.09 mm, respectively. Paired t-tests showed that the mean error between subject groups was 0.05 +/- 0.15 mm indicating that there was no difference between the two subject groups (p = 0.18). CONCLUSION: The technique as described is clinically reproducible for children and adults and can be used for studies assessing facial changes due to growth or clinical intervention.

Demonstration of antibodies to the chitin-binding mistletoe lectin (cbML) in tumor patients before and during therapy with an aqueous mistletoe extract.

Mistletoe extracts exert immunomodulatory properties in vivo and in vitro, and these effects have been related mainly to mistletoe lectin 1 (ML-1). Recently, a new chitin-binding mistletoe lectin (cbML) has been isolated and structurally characterized in these extracts. Aim of the present study was, therefore, to evaluate whether this cbML also affects immunocompetent cells and can for instance activate B-cells to produce anti-cbML-specific antibodies. Sera from patients with different tumors who were treated with the mistletoe extract ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9, 12, 18, and 24 weeks. Sera were tested by ELISA against ML-1, -3, and cbML, isolated from a single mistletoe plant collected from an apple tree (Malus domestica). Eight of the 26 patients (31%) had IgG anti-cbML antibodies already before therapy, while only four had anti-ML-1 and -3 antibodies. Of the 18 anti-cbML negative patients before therapy 54% developed these antibodies during therapy, and there was a significant increase in anti-cbML antibody titers. In contrast, anti-ML-1 or -3-antibodies developed in almost 100% of the 25 patients being negative before therapy. These data indicate that cbML can induce immunological responses in patients treated with mistletoe extracts, although it seems to have lower antigenicity. Interestingly, anti-cbML antibodies can be observed in a low incidence also in individuals, not having yet received mistletoe therapy.

Induction of antibodies to viscotoxins A1, A2, A3, and B in tumour patients during therapy with an aqueous mistletoe extract.

Mistletoe extracts exert immunomodulatory properties on immunocompetent cells of the innate as well as the specific immune system. These effects have been mainly ascribed to mistletoe lectin 1 (ML-1) present in most of the extracts. However, it became evident that also other components of these extracts may induce immunological reactions, and especially viscotoxins (VT) may be of relevance. Aim of the study was, therefore, to evaluate whether VT like ML-1 could activate B-cells and lead to the production of VT-specific antibodies. Sera from 26 patients with different tumours who were treated with the mistletoe extract ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9, 12, and 18 weeks. Sera were tested by ELISA against the four viscotoxins A1, A2, A3, B, as well as against ML-1. Within the observation period twenty-four (92%) of the 26 patients developed antibodies to at least one of the four VT and 25 (96%) to ML-1. In most instances, anti-VT antibodies appeared after 6-9 weeks of treatment. The antibodies were predominantly of the IgG type belonging preferentially to the IgG1 and IgG3 subclass. IgE antibodies were found only to VT-B and to ML-1. There was no relation between the development of antibodies to VT and ML-1, and also cross-reactivity could be excluded with high probability. These data indicate that not only ML-1 but also VT induce immunological responses in patients treated with mistletoe extracts. Whether there is any relationship to the postulated anti-tumour effect of mistletoe extracts has, however, still to be evaluated.

Effects of a mistletoe preparation with defined lectin content on chronic hepatitis C: an individually controlled cohort study.

Despite advances in the therapy of chronic hepatitis C for some hepatitis C virus (HCV) genotypes interferon and ribavirin combination therapy is effective in less than 50% of patients. Abnobaviscum Quercus (AQ) is a mistletoe preparation containing defined amounts of mistletoe lectins (ML). It has shown immunomodulatory properties in vitro and in vivo. In small clinical trials AQ resulted, within an anthroposophical treatment concept, in a biochemical or virological response in up to 40% of patients with chronic hepatitis C. In order to evaluate the effect of this preparation we conducted an individually controlled cohort study. 25 patients with chronic hepatitis C (mean duration 147 +/- 80 months) and elevated alanine aminotransferase (ALT) levels were included in the study. As control they were observed for 6 months pre-treatment. This pre-treatment period was followed by 6 months of active treatment in which the mistletoe preparation was subcutaneously injected three times a week. Main outcome parameters were normalization of ALT and viral load. Hepatitis C associated signs and symptoms like tiredness, fullness in the right upper abdomen and musculoskeletal pain were assessed monthly in a standardized questionnaire. All 25 patients completed the study and most of the patients wanted to continue treatment. Mean duration of treatment was 9.1 months. None of the patients had complete or partial normalization of ALT or HCV RNA levels during pre-treatment or treatment period. Mean ALT did not change during the study. Tiredness, fullness in the right upper abdomen and musculoskeletal pain were present in 18, 8 and 4 patients respectively. They significantly improved within two months of treatment. A significant eosinophilia (p=0.0001) occurred between month 2 and 6 during treatment. 9 month treatment with a ML containing mistletoe preparation has no effect on viral load or ALT as markers of activity in patients with chronic hepatitis C. However, frequency and intensity of clinical signs and symptoms in our patients decreased significantly, similar to reports of improved quality of life in tumour patients treated with such preparations. A significant eosinophilia suggests that ML containing mistletoe preparations induce a T-helper 2 immune response.

[The effect of mistletoe lectins on the limulus amebocyte lysate test]. / Beeinflussung des Limulus-Amöbozyten-Lysat-Tests durch Mistel-Lektine.

Former reports about too high and from batch to batch changing endotoxin contents in mistletoe preparations and phytopharmaceuticals for parenteral administration correlated with clinically observed side effects led to investigations of the endotoxin content of ABNOBA-viscum. For that purpose the endotoxin levels of the raw materials, the equipment and the production steps were observed by using the limulus amebocyte lysate (LAL) test. The mean value found in the preparation containing the highest available concentration (dilution level 2 containing 15 mg of plant extract from 20 mg of fresh mistletoe in 1 ml) came to 66.7 endotoxin units (EU) per ml, corresponding to about one fifth of the commonly accepted limit value of 350 EU/ml, the human pyrogenic dose. Depending on their dilution level, lower concentrated preparations led also to lower LAL test results. It could be proved that lectins contained in mistletoe preparations cause false positive LAL tests. Such results implicate false too high contents of endotoxin. Different lysates, i.e. Limusate, Pyrogel, Pyrogent, and Pyroquant showed approximately the same results. Microbiological and LAL test results indicate that only 10% of the total amount of the LAL test result was caused by endotoxins. So it is necessary to form a new estimation of the former results of determination of the endotoxin content of mistletoe preparations.

A simple model for calculating residential 60-Hz magnetic fields.

A model is presented that permits the calculation of densities of 60-Hz magnetic fields throughout a residence from only a few measurements. We assume that residential magnetic fields are produced by sources external to the house and by the residential grounding circuit. The field from external sources is measured with a single probe. The field produced by the grounding circuit is calculated from the current flowing in the circuit and its geometry. The two fields are combined to give a prediction of the total field at any point in the house. A data-acquisition system was built to record the magnitude and phase of the grounding current and the field from external sources. The model's predictions were compared with measurements of the total magnetic field at a single location in 23 houses; a correlation coefficient of .87 was obtained, indicating that the model has good predictive capability. A more detailed study that was carried out in one house permitted comparisons of measurements with the model's predictions at locations throughout the house. Again, quite reasonable agreement was found. We also investigated the temporal variability of field readings in this house. Daily magnetic field averages were found to be considerably more stable than hourly averages. Finally, we demonstrate the use of the model in creating a profile of the magnetic fields in a home.

Comparison of intramuscular recombinant alpha interferon (rIFN-2A) with topical acyclovir for the treatment of first-episode herpes genitalis and prevention of recurrences.

Intramuscular recombinant alpha interferon (rIFN-2A; 9 million IU given for 5 days during a 9-day treatment period) was compared with topical acyclovir in a double-blind, placebo-controlled trial for the treatment of first-episode genital herpes simplex virus (HSV) infection and for subsequent alteration of the frequency of recurrences. rIFN-2A (within 96 h of onset of the first episode) was not superior to topical acyclovir in a well-matched group of 105 patients. The early use of rIFN-2A also did not alter the frequency or severity of genital HSV recurrences within either the first or second 6 months following therapy. Separate analyses by HSV type and by type of infection (primary versus nonprimary) did not change this conclusion. Furthermore, there was significant toxicity associated with rIFN-2A therapy. rIFN-2A is not indicated for the treatment of genital HSV infections.

Serum concentration and dose-response relationships for carprofen in rheumatoid arthritis.

Thirty-eight patients with active, definite, or classical rheumatoid arthritis were tested in a double-blind, 3-week-per-arm, multiple-crossover, randomized, block-design comparison of 100, 300, 600, and 800 mg/day carprofen given b.i.d. A linear dose-response relationship was demonstrated for six of nine efficacy measures (p less than 0.052). A plasma concentration to therapeutic response relationship was shown just before or 1 to 2 hours after a dose (p less than 0.05) for seven efficacy parameters for the patients with at least three serum carprofen concentrations. By nonparametric analysis, with the patients divided into three equal groups, the percent of responders rose from 38.1% to 50% to 59.1%. Sixty-nine percent of patients responded when carprofen concentrations were greater than 10 micrograms/ml, whereas only 9% responded when they were below 1.9 micrograms/ml. Although only seven patients had limiting side effects, there was a tendency toward a dose-toxicity relationship through 600 mg daily carprofen.

[Microbial growth in mixed-bed ion exchange columns]. / Uber die Verkeimung von Mischbett-Ionenaustauschern.

The microbial growth in ion-exchange columns of Christ GmbH Leonberg (Germany) was studied under differing water processing conditions. Continuous processing led to the same or slightly higher microbial counts in the product water compared to the feed water. Feeding the considerably contaminated column with slightly contaminated water (less than 40 CFU/100 ml) also didn't prevent microbial growth in the column. If water was withdrawn on demand only, an overnight no-demand period with closed inlet of the column led to considerable microbial growth, raising the microbial counts of the product water to well above the feed water level. But lower microbial counts were found in the product water than in the feed water by tightly closing the outlet of the column and hereby keeping the column at the same pressure as exists in the piping system. This was observed in several months long experiments operating with disinfected as well as freshly regenerated resin. The passage through a column of freshly regenerated resin led to a germ reduction of approximately 2 powers of ten and to an elimination of pyrogens.

Therapy of genital herpes with topically applied interferon.

Ninety-four patients with recurrences of genital herpes were randomized in a double-blind trial to receive topical therapy for 5 days with either alpha-2a interferon at 30 X 10(6) IU/ml or 10 X 10(6) IU/ml or placebo six times daily. No differences were noted between either interferon dose and placebo with respect to the duration of viral shedding, the time to crusting, or the time to healing of herpetic lesions. Aqueous solutions of alpha-2a interferon applied topically to unroofed vesicles do not appear to be clinically useful in the treatment of recurrences of genital herpes.

Myocardial mucormycosis with emboli in a hemodialysis patient.

A 32-year-old man was found to have disseminated mucormycosis. Echocardiogram demonstrated bilateral ventricular thrombi, but there were no segmental wall motion abnormalities. At autopsy, it was found that these thrombi originated from a myocardial abscess and that death had been caused by septic embolization to the brain. The patient had been on maintenance hemodialysis for 9 years. Two transplants, 7 and 8 years previously, had been unsuccessful and had involved only 3 weeks of immunosuppressive treatment. No factor predisposing to fungal infection could be identified, with the possible exception of chronic uremia.