Acupuncture in diabetic peripheral neuropathy-protocol for the randomized, multicenter ACUDPN trial.

BACKGROUND: Acupuncture is used to treat patients with diabetic peripheral neuropathy; however, the evidence is unclear. We present the design and methodology of the ACUDPN (ACUpuncture in Diabetic Peripheral Neuropathy) trial, which investigates the effectiveness of acupuncture for the treatment of diabetic peripheral neuropathy (DPN) symptoms. The aim of this study is to investigate whether acupuncture is effective for the treatment of DPN symptoms. METHODS: This study is a two-armed, randomized, controlled, parallel group, open-label, confirmatory, multicenter trial (8-week intervention period plus 16 weeks of follow-up). Physicians in outpatient units in Germany who specialize in acupuncture treatment will treat 110 diabetes type II patients with clinical symptoms of peripheral neuropathy in the feet and legs with signs of neuropathy according to nerve conduction testing. The patients will be randomized in a 1:1 ratio to one of the following two groups: (a) semi-standardized acupuncture plus routine care or (b) routine care alone. Acupuncture will consist of 12 treatments per patient over 8 weeks. The primary outcome will be the overall DPN-related complaints in the extremities after 8 weeks as measured by the Visual Analog Scale (VAS). Further outcome measures will include DPN-related pain, the Neuropathic Pain Symptom Inventory (NPSI), Diabetic Peripheral Neuropathic Pain Impact (DPNPI) scores, and nerve conduction parameters of the sural nerve at weeks 8, 16, and 24. DISCUSSION: The results of this trial will be available in 2021 and will help clarify whether acupuncture can be considered effective for the treatment of DPN with regard to the subdimensions of the neuropathic clinical picture. TRIAL REGISTRATION: ClinicalTrials.gov NCT03755960 . Registered on 11 August 2018.

Dose-titration effects of fish oil in osteoarthritic dogs.

BACKGROUND: Food supplemented with fish oil improves clinical signs and weight bearing in dogs with osteoarthritis (OA). OBJECTIVE: Determine whether increasing the amount of fish oil in food provides additional symptomatic improvements in OA. ANIMALS: One hundred and seventy-seven client-owned dogs with stable chronic OA of the hip or stifle. METHODS: Prospective, randomized clinical trial using pet dogs. Dogs were randomly assigned to receive the baseline therapeutic food (0.8% eicosopentanoic acid [EPA] + docosahexaenoic acid [DHA]) or experimental foods containing approximately 2- and 3-fold higher EPA+DHA concentrations. Both veterinarians and owners were blinded as to which food the dog received. On days 0, 21, 45, and 90, serum fatty acid concentrations were measured and veterinarians assessed the severity of 5 clinical signs of OA. At the end of the study (day 90), veterinarians scored overall arthritic condition and progression of arthritis based on their clinical signs and an owner interview. RESULTS: Serum concentrations of EPA and DHA rose in parallel with food concentrations. For 2 of 5 clinical signs (lameness and weight bearing) and for overall arthritic condition and progression of arthritis, there was a significant improvement between the baseline and 3X EPA+DHA foods (P=.04, .03, .001, .0008, respectively) but not between the baseline and the 2X EPA+DHA foods. CONCLUSIONS AND CLINICAL IMPORTANCE: Increasing the amount of fish oil beyond that in the baseline food results in dose-dependent increases in serum EPA and DHA concentrations and modest improvements in the clinical signs of OA in pet dogs.

Thalamic volume in first-episode and chronic schizophrenic subjects: a volumetric MRI study.

OBJECTIVE: The thalamus, as a composite of several functionally very different nuclei, is a major relay and filter station in the CNS and is significantly involved in information processing and gating. The aim of our study is to investigate first-episode and chronic patients and controls to shed light on the potential pathogenetic role of the thalamus in schizophrenia and to assess the relationship between thalamic volumes and psychopathology ratings. METHODS: Forty-three male right-handed chronic and 25 male right-handed first-episode schizophrenic patients treated at the psychiatric hospital of the Ludwig-Maximilians University in Munich and 50 male control subjects were enrolled into the study. Demographic information and current symptom profile of all schizophrenic subjects were assessed using a semistructured interview, including a variety of measures relevant to the study. Volumetry of the thalamic gray and white matter was obtained with 1.5 T MRI, using the BRAINS software application. RESULTS: No significant differences regarding thalamic volumes were detected across groups. However, negative symptoms were significantly correlated with thalamic volumes in first-episode patients, whereas duration of illness and extrapyramidal symptoms were related to thalamic volumes in chronic patients. SUMMARY: Our findings indicate that, while the thalamus might be involved in the pathogenesis of negative symptoms, thalamic volume reduction is not a required element in the pathophysiology of the schizophrenic phenotype.

[Initial experiences with adjuvant locoregional radioimmunotherapy using 131I-labeled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)]. / Initiale Erfahrungen mit der adjuvanten lokoregionalen Radioimmuntherapie mit 131I-markierten monoklonalen Tenascin-Antikörpern (BC-4) bei Patienten mit Gliom (WHO III und IV).

AIM: None of the established treatments (surgery, radiotherapy, chemotherapy) for malignant glioma has improved its very poor prognosis. Adjuvant locoregional radio-immunotherapy (RIT) represents a new therapeutic approach. We present our initial experience with this therapeutic tool with respect to adverse effects, biokinetics and clinical follow-up. METHODS: Following surgery and radiotherapy, 12 patients with glioma (4, WHO stage III; 8, WHO stage IV) underwent 1-5 RIT-cycles (average dose 1100 MBq 131labelled monoclonal BC-4 antibodies) at six week intervals. Follow-up included serial FDG-PET and MRI investigations. Evaluation of biokinetics included whole body scans, together with analysis of blood, urine and fluid from the tumor cavity. RESULTS: Following RIT, four patients experienced temporary seizures, which, in one case, were associated with temporary aphasia. Eight patients developed HAMA (human anti-mouse antibodies) during follow-up. Mean biologic half-life of the radiopharmaceutical in the resection cavity was 3.9 d (range: 1.0-10.2 d) and remained stable intraindividually during further RIT-cycles. The antibody/radionuclide conjugate remained stable in the tumor cavity for at least 5 d. Median survival presently stands at 18.5 months compared to 9.7 months in a historical patient group (n = 89) undergoing conventional therapeutic strategies. Five patients show no signs of recurrence. In three patients with post-surgical evidence of residual tumor, one patient showed partial remission, one stable disease, and one progressive disease during RIT. Four patients without evidence of residual tumor mass at the beginning of RIT developed recurrence during therapy. CONCLUSIONS: Initial experience demonstrates that locoregional RIT is a well tolerated treatment modality that may represent a promising new approach in the management of patients with malignant glioma. Advantages of local application include passage of the blood-brain barrier, high concentration of activity within the resection cavity and low systemic toxicity.

Regional differences in peptide degradation by rat cerebral microvessels: a potential novel regulatory mechanism for communication between blood and brain.

The blood-brain barrier (BBB), composed of the microvessels of cerebral capillary endothelial cells, regulates the passage of peptides into the brain in several ways, mainly by saturable transport or passive diffusion. Here we describe an additional mechanism by which this regulatory function can occur. Cerebral microvessels were isolated from different regions of the brain and incubated with the mu-opiate selective endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) or the opiate-modulating Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), both tetrapeptides selectively tritiated at the Pro. Degradation was determined by HPLC. For both peptides, the metabolism by microvessels from the cerebral cortex was much greater than that by microvessels from the hypothalamus or pons. For endomorphin-1, the least degradation was in the pons; for Tyr-MIF-1 there was no difference in metabolism by microvessels from the pons or hypothalamus. The results show a novel mechanism at the BBB by which the BBB can selectively regulate the activity of different peptides in different regions of the brain.

Spiritual care: bridging the disciplines in congregational health ministries.

These materials describe the professional, legal, relational, and theological roles of parish nurses, health care chaplains, and community clergy. It illustrates these roles by discussing two case studies of how these professionals can work together. It then provides examples of role violations for each profession and recommends some simple rules that will enable them to work together productively.

Adhesio interthalamica in male patients with schizophrenia.

OBJECTIVE: The authors investigated whether absence of the adhesio interthalamica in patients with schizophrenia constitutes a marker of early developmental neuropathological changes. METHOD: Thirty male patients with schizophrenia and 30 healthy male subjects were recruited for study. Magnetic resonance imaging was performed, and the presence or absence of the adhesio interthalamica was determined for each subject. The length and volume of the third ventricle were also measured. RESULTS: No differences in the presence or absence of the adhesio interthalamica were found between patients with schizophrenia and normal comparison subjects. Patients without the adhesio interthalamica had significantly higher scores for negative symptoms than patients with the adhesio interthalamica. There was no correlation between absence of the adhesio interthalamica and length and volume of the third ventricle in either patients or comparison subjects. CONCLUSIONS: The findings suggest that patients with schizophrenia who do not have the adhesio interthalamica are characterized by more severe negative symptoms.

The use of colonic irrigation to control fecal incontinence in dogs with colostomies.

OBJECTIVE: To determine if once-daily colonic irrigation results in fecal continence for a 24-hour period in dogs with colostomies and if colonic volume increased in response to the irrigation. STUDY DESIGN: A prospective controlled experimental study. ANIMALS: Four intact male and one intact female mixed breed dogs. MATERIALS: All dogs received left end-on paralumbar colostomies. Four dogs received once-daily colonic irrigation for 8 weeks, whereas the control dog did not. Daily fecal weights were recorded for the length of the study in all dogs. Barium enema studies and volumetric studies were used to determine colonic volumes. RESULTS: Daily fecal weights were significantly decreased in treatment dogs compared with the control dog. Colonic volume increased in irrigated dogs in response to daily irrigation over the 8 week period of the study. CONCLUSIONS: Colonic irrigation resulted in significantly decreased fecal production over a 24-hour period. Therefore management of dogs with colostomies would be more practical and cost effective. It did not result in complete fecal continence in this study. Further clinical studies are indicated to determine if longer periods of irrigation would result in complete continence.

hpaA mutants of Xanthomonas campestris pv. vesicatoria are affected in pathogenicity but retain the ability to induce host-specific hypersensitive reaction.

Xanthomonas campestris pv. vesicatoria is the causal agent of bacterial spot disease on pepper and tomato plants. We reported previously that the main hrp (hypersensitive reaction and pathogenicity) gene cluster in X. c. pv. vesicatoria contains six transcription units, designated hrpA to hrpF. We present here the sequence of the hrpD operon and an analysis of non-polar mutants in each of the six genes. Three genes, hrcQ, hrcR and hrcS, are predicted to encode conserved components of type III protein secretion systems in plant and mammalian pathogenic bacteria. For hrpD5 and hrpD6, homologues have only been found in Ralstonia solanacearum. Interestingly, the hrpD operon contains one gene, hpaA (for hrp-associated), which is specifically required for disease development. hpaA mutants are affected in pathogenicity, but retain in part the ability to induce avirulence gene-mediated, host-specific hypersensitive reaction (HR). In addition, HpaA was found to contain two functional nuclear localization signals, which are important for the interaction with the plant. We propose that HpaA is an effector protein that may be translocated into the host cell via the Hrp secretion pathway.

[123I]IBZM SPECT in patients treated with typical and atypical neuroleptics: relationship to drug plasma levels and extrapyramidal side effects.

[123I]Iodobenzamide (IBZM) is an iodine-labeled dopamine receptor ligand and can be used to visualize brain D2 receptors in humans with single photon emission computerized tomography (SPECT). The ratio of striatal IBZM uptake to uptake in frontal cortex (ST/FC ratio) represents a semiquantitative measure of D2 receptor binding in the striatum. Our study sample included six patients treated with haloperidol (3.0-8.0 mg/day orally; one patient with an average of 0.9 mg/day intramuscularly), five patients with benperidol (9.0-15.0 mg/day orally) and nine patients treated with clozapine (200.0-600.0 mg/day orally). Typical neuroleptics (TNs) and atypical neuroleptics (ANs) were significantly different in their ST/FC ratios. The ST/FC ratios indicated that patients treated with benperidol exhibited the lowest ST/FC ratios, with increasingly higher ratios in patients on haloperidol or clozapine. We found a curvilinear relationship between the ST/FC ratios and the dose/kg body wt. of TNs and ANs on the basis of a dose-normalization according to Ki-values of the neuroleptic at D2 receptors and a weaker, but also curvilinear relationship between ST/FC ratios and normalized dosages according to clinically defined chlorpromazine equivalents. The specific uptake of IBZM did not correlate with the plasma levels of the TN haloperidol at the present dose range (0-12.4 ng/ml). For clozapine, a meaningful negative correlation between plasma levels and ST/FC ratio could be established. There was a negative continuous correlation between uptake of IBZM and extrapyramidal side effects, which is different from the threshold-based relationship between extrapyramidal side effects and IBZM uptake reported previously.

Dose response and time course of carboplatin-induced micronucleated polychromatic erythrocytes in the cat: implications for combination carboplatin chemotherapy.

The dose response and time course of micronucleated polychromatic erythrocytes (mPCE) in cat peripheral blood induced by various doses (150-250 mg/m2) of carboplatin in vivo was determined. The data indicate that carboplatin produced a significant (p < 0.05) dose-dependent increase in the number of mPCE over baseline values; however, the times following carboplatin administration when mPCE were first observed differed significantly (p < 0.05) between the three carboplatin dose groups. mPCE were present in significantly greater numbers (p < 0.05) on smears at an earlier time interval following a single carboplatin dose of 150 mg/m2 than for a dose of either 200 or 250 mg/m2. The peak number of mPCE occurred on days 7, 14 and 17.5 following administration of a carboplatin dose of 150, 200 and 250 mg/m2, respectively. The pattern of time course delay following carboplatin administration suggests that the block of erythropoietic stem cells in G2 is dose dependent. Indeed, the administration of carboplatin arrested the cell cycle in the G2 phase and, at higher doses, diminished the number of cycling erythroid precursor cells. mPCE were apparent in blood smears only after recovery from this arrest and resumption of replication. This observation has implications for the scheduling of carboplatin administration when used in combination with other anticancer drugs.

Octreotide scintigraphy and catecholamine response to an octreotide challenge in malignant phaeochromocytoma.

OBJECTIVE: Octreotide scintigraphy has been reported to visualize chromaffine tumours. This study in patients with malignant phaeochromocytoma was designed to assess octreotide in comparison with standard m-iodobenzylguanidine (MIBG) scintigraphy and to study functional activity of somatostatin receptors. Finally, two cases of octreotide treatment are reported. DESIGN: Open, prospective clinical trial. PATIENTS: In 12 patients with histologically proven malignant phaeochromocytoma, 111In-octreotide scintigraphy, 123I-MIBG scintigraphy and computed tomography were performed. In ten patients plasma catecholamine response to a single dose of octreotide (200 micrograms i.v.) was monitored up to 5 hours after injection. Two patients were treated with octreotide over several months. MEASUREMENTS: Plasma catecholamines were measured by high performance liquid chromatography (HPLC). Scintigraphy was performed using a large field gamma camera and SPECT technique where appropriate. RESULTS: At least one metastatic lesion was visualized by octreotide scintigraphy in eight patients while the remaining four patients had negative findings. In total, 43 out of 54 known metastases (79.6%) were detected by MIBG, 24 (44.4%) by octreotide. Nevertheless, octreotide scintigraphy detected six metastases that were negative by MIBG. There was no correlation between the results of octreotide scintigraphy and catecholamine suppression after i.v. octreotide. In two patients on octreotide treatment, symptomatic improvement, but not mass reduction, could be documented. CONCLUSIONS: Octreotide scintigraphy behaves in part complementary to MIBG, thus, increasing diagnostic sensitivity. Presence of somatostatin receptors, as demonstrated by octreotide scintigraphy, does not necessarily predict functional activity or therapeutic response.

Infections with various types of organisms stimulate transcription from a short promoter fragment of the potato gst1 gene.

By histochemical GUS staining, we demonstrate that transcription from a short promoter fragment of the potato gst1 gene is locally induced after infection of a host plant with various types of pathogenic or symbiotic organisms. This regulatory unit is not active in noninfected tissues, except root apices and senescing leaves. Measuring the expression of a fusion between the promoter fragment and the gus gene in transgenic plants, therefore, allows comparison of the induction of defense reactions in different types of plant-microbe interactions, in one and the same plant.

Pathogen-defence gene prp1-1 from potato encodes an auxin-responsive glutathione S-transferase.

Genetic studies have previously implicated the prp1 gene family in the defence of potato against infection with the late blight fungus Phytophthora infestans. Here, we show that the concentrations of PRP1 mRNA as well as protein rapidly increase in potato leaves after fungal infection and stay at high levels during an extended period of the infection cycle. After separation of subcellular components by differential centrifugation, PRP1 protein was identified in the cytosolic fraction. Expression studies with chimeric promoter/beta-glucuronidase gene constructs in transgenic potato plants provided evidence that transcription of the prp1-1 gene, representing one member of the prp1 gene family, is at least partly responsible for the accumulation of PRP1 mRNA and protein upon fungal infection. After expression of the prp1-1-coding sequence in Escherichia coli, the corresponding 26-kDa protein exhibited glutathione S-transferase activity with Km values of 9.8 mM and 0.11 mM for the artificial standard substrate 1-chloro-2,4-dinitrobenzene and glutathione, respectively. Photoaffinity labeling of the protein with tritiated 5-azido-indole-3-acetic acid suggested that the phytohormone indole-3-acetic acid or a structurally related compound serve as a regulator or substrate of the prp1-1 encoded glutathione S-transferase. This assumption was further supported by the inhibitory effect of the phytohormone on the enzyme activity in vitro. The implications of these findings for a potential involvement of indole-3-acetic acid in the control of defence reactions are discussed.

Evaluation of pain and irritation following local administration of parenteral formulations using the rat paw lick model.

Water miscible cosolvents in parenteral products generally increase pain and/or local irritation post injection. The goal of this study was to validate the usefulness of the rat paw lick model (Cleozzi et al., J. Pharmacol. Meth., 4, 1980, 285-289) in screening pain and local irritation with parenteral formulations. Paw licks were counted in 3 min. intervals, over a total period of 15 min., following subplantar injection of test formulations in the hind paw of rats. A dose-response relationship following the injection of solutions containing increasing concentrations of a known painful compound was used to validate the model. The results obtained from additional experiments were found to correlate closely to those obtained using other tests (e.g. in vitro hemoglobin release test, and in vivo creatine kinase release test in rabbits). It was found that: (a) the model is responsive to changes in the sensation of pain and/or irritation due to drug or non-active components; (b) the increase in propylene glycol or ethanol concentrations results in increased pain and/or local irritation, (c) the increase in the apparent pH of cosolvent-based formulations from 7.2 to > or = 10 may increase pain and/or local irritation, and (d) there is generally a "thresh-hold limit" between the concentration of painful component and the paw licks, which should be established for the component under evaluation. The data overall suggest that the rat paw lick model is a rapid and simple method for rapid screening of formulations for pain/irritation following local administration.

[1H-NMR study of the OR1 operon in bacteriophage lambda. I. Assignment of signals from imino protons and adenine C2 protons]. / Izuchenie metodom 1H-IaMR operatora OR1 bakteriofaga lambda. I. Otnesenie signalov iminoprotonov i C2-protonov adenina.

An oligodeoxyribonucleotide composed of 17 residues, d(TATCACCGCCAGAGGTA), and a complementary chain were synthesized. Their duplex was identical with the operator OR1, the binding site for bacteriophage lambda cro and c1 repressors. The 1H NMR spectra (500 MHz) of the duplex imino and aromatic protons were studied at 10, 20 and 25 degrees C. Signals from the imino protons of complementary base pairs and from the C2 protons of adenine (with the exception of the duplex terminal nucleotides) were assigned using the NOE technique and the known characteristics of short DNA fragment melting. No signals from the imino protons of the terminal base pairs were detected even at 10 degrees C due to fraying which increased as the temperature was raised. The assignment of signals can be used to identify centers of interaction between the operator OR1 and repressors, as well as to study possible local changes in DNA geometry.

[The psoriatic bone manifestation]. / Die psoriatische Osteopathie.

Besides the known joint involvement as seen in the whole-body scan which uses 99m technetium-phosphate-complexes, skeletal scintigraphic investigations in 17 patients with psoriasis have demonstrated circumscribed or diffuse accumulative pathological concentrations of the radionuclide within the skeleton of the skull, the thyroid cartilage, the bony thorax and osseous long bones. These pathological accumulations of radionuclides of TcP-complexes which are distant from joint regions, point to proliferative phenomena in the bone in case of psoriasis especially in alterations of the collagenous metabolism.