Effects of endogenous and exogenous cholecystokinin and of infusion with the cholecystokinin antagonist L-364,718 on pancreatic and gastrointestinal growth

Continuous subcutaneous infusion of cholecystokinin (CCK-8; 5 micrograms/kg/h) to rats for 7 weeks raised the plasma CCK concentration almost fivefold and increased the pancreatic weight by about 50% but was without effect on the gastrointestinal tract. Continuous subcutaneous infusion of the CCK antagonist L-364,718 (200 micrograms/kg/h) for 7 weeks reduced the weight of the pancreas by about 30% but was without effect on the gastrointestinal tract. The effect of continuous subcutaneous infusion of CCK-8 and L-364,718 in combination was very similar to that of L-364,718 alone. Pancreaticobiliary diversion (PBD) induced a nearly 10-fold increase in the plasma CCK concentration 3 and 7 weeks after the operation. The serum gastrin values were unaffected. The weight of the pancreas was more than doubled after 7 weeks. At the same time the small intestine had gained weight, but the colon was unaffected. Continuous subcutaneous infusion of L-364,718 prevented the effect of PBD on the pancreas. On the basis of the assumption that L-364,718 is a specific antagonist of CCK, we conclude that endogenous CCK has a trophic effect on the pancreas but not on the gastrointestinal tract and that it is essential for normal pancreatic growth.     

Human cytomegalovirus gH/gL/UL128/UL130/UL131A complex elicits potently neutralizing antibodies in mice

Human cytomegalovirus (HCMV) is a member of the β-herpesvirus family that causes significant disease worldwide. Although evidence exists that neutralizing antibodies and cytotoxic T cell responses to HCMV antigens can prevent HCMV disease and/or infection, there are no approved vaccines to prevent HCMV disease. Over the past 10 years, multiple HCMV vaccines have been tested in man but only partial protection has been achieved in these studies. HCMV contains multiple surface-expressed glycoproteins that are critical to viral entry, including gB, the gM/gN complex, the gH/gL complex, and a pentameric gH/gL/UL128/UL130/UL131A complex. Recently we showed that viral replicon particles (VRPs) expressing the gH/gL complex elicited more potently neutralizing antibodies than VRPs expressing gB in mice. Here we compare the immunogenicity of VRPs encoding the HCMV gH/gL and pentameric complexes, as well as purified gH/gL and pentameric complexes administered in the presence or absence of the MF59 adjuvant. The results of these studies indicate that the pentameric complex elicits significantly higher levels of neutralizing antibodies than the gH/gL complex, and that MF59 significantly increases the potency of each complex. In addition, we show that animals immunized with pentamer encoding VRPs or the pentameric subunit produce antibodies that recognize a broad range of antigenic sites on the complex. Taken together, these studies support the utility of the pentameric complex in HCMV vaccine candidates.     

A clinical crossover trial of the effect of manipulative therapy on pain and passive and active range of motion of the painful hip

ObjectivesThis study aims to determine whether manipulative therapy of the hip joint can increase range of motion (ROM) and/or decrease pain in individuals experiencing symptomatic hip pain.MethodsNon-disabled young adults were recruited on campus of a chiropractic college for this randomized crossover study. Subjects’ hip active and passive ROM and pain perception were measured. Subjects then received a drop-piece hip manipulation (DPHM) or an alternative treatment, followed by measurement of active and passive ROM and pain.ResultsEight males and 12 females (n=20) between the ages of 21–32 years completed the study. Statistically significant improvements in numeric pain scale (NRS) and passive abduction were observed for the manipulation group when compared to the alternative treatment. No significant change was observed for all other hip ranges.ConclusionsDPHM of the symptomatic hip joint in a small sample of young adults resulted in statistically significant improvements in pain and passive abduction when compared to sham manipulation. Due to low sample size, further research is recommended.     

Newborn behaviour to locate the breast when skin‐to‐skin: a possible method for enabling early self‐regulation

Aim: The aim of this study was to provide a more detailed analysis of the infant’s behavioural sequence that begins immediately after birth and terminates with grasping the nipple, suckling and then falling asleep. Method: Twenty‐eight full‐term infants were videotaped immediately after birth. A video protocol was developed to examine infant behaviours identified from five random videotapes. Results: When birth crying had stopped, the babies showed a short period of relaxation and then successively became alert. They went through an ‘awakening phase’, an ‘active phase’ with movements of limbs, rooting activity and looking at the mother’s face, a ‘crawling phase’ with soliciting sounds, a ‘familiarization phase’ with licking of the areola, and a ‘suckling phase’ and last a ‘sleeping phase’. Five factors related to the time spent to locate the breast: more number of looks at the breast 10–20 min after birth (p < 0.0001); and exposure to meperidine (p = 0.0006) related to increased time. Early start of crawling (p = 0,0040); increased number of ‘soliciting sounds’ (p = 0.0022); and performing hand–breast–mouth movements (p = 0.0105) related to shorter time. Conclusion: Inborn breastfeeding reflexes were depressed at birth, possibly because of a depressed sensory system. It is hypothesized that when the infant is given the option to peacefully go through the nine behavioural phases birth cry, relaxation, awakening, activity, crawling, resting, familiarization, suckling and sleeping when skin‐to‐skin with its mother this results in early optimal self‐regulation.     

Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer.

PURPOSE: To better direct targeted therapies to the patients with tumors that express the target, there is an urgent need for blood-based assays that provide expression information on a consistent basis in real time with minimal patient discomfort. We aimed to use immunomagnetic-capture technology to isolate and analyze circulating tumor cells (CTC) from small volumes of peripheral blood of patients with advanced prostate cancer. EXPERIMENTAL DESIGN: Blood was collected from 63 patients with metastatic prostate cancer. CTCs were isolated by the Cell Search system, which uses antibodies to epithelial cell adhesion marker and immunomagnetic capture. CTCs were defined as nucleated cells positive for cytokeratins and negative for CD45. Captured cells were analyzed by immunofluorescence, Papanicolau staining, and fluorescence in situ hybridization. RESULTS: Most patients (65%) had 5 or more CTCs per 7.5 mL blood sample. Cell counts were consistent between laboratories (c = 0.99) and did not change significantly over 72 or 96 h of storage before processing (c = 0.99). Their identity as prostate cancer cells was confirmed by conventional cytologic analysis. Molecular profiling, including analysis of epidermal growth factor receptor (EGFR) expression, chromosome ploidy, and androgen receptor (AR) gene amplification, was possible for all prostate cancer patients with >or=5 CTCs. CONCLUSIONS: The analysis of cancer-related alterations at the DNA and protein level from CTCs is feasible in a hospital-based clinical laboratory. The alterations observed in EGFR and AR suggest that the methodology may have a role in clinical decision making.     

Amino acid transport across the placenta measured by positron emission tomography and analyzed by compartment modelling

The materno-fetal transfer of methionine in the Rhesus monkey was investigated using positron emission tomography, a non-invasive in vivo tracer technique based on short-lived radionuclides. A bolus dose of [11CH3]-l-methionine was administered intravenously and the radioactivity concentrations in the placenta, the fetus and the maternal arterial blood were measured as functions of time and fitted to an equation derived from a four compartment model of the feto-placental complex. Rate constants were calculated describing maternal placental blood flow, the transfer of [11CH3]-l-methionine to the placental tissue and the fetus. The transfer rate of methionine to the fetus was estimated as 0.8-1.5 nmol/min/g placenta and was similar to the transfer to the placental tissue. An approximate blood flow through the intervillous space of 128 ml/min was found. The correlation between placental transfer to the fetus and the maternal blood flow in the intervillous space was low.     

Evaluation of the effect of high-energy proton irradiation treatment on meningiomas by means of 11C-L-methionine PET

A remnant meningioma of WHO grade I that is located at the base of the skull and is treated with radiotherapy has to be followed up for at least 5-10 years to evaluate the treatment effect and detect recurrence. The tumour has to grow considerably to show detectable volume increase on computed tomography (CT) or magnetic resonance imaging (MRI). Owing to the location at the base of the skull, a small increase in tumour volume may be hazardous. It is thus important to find a method to evaluate treatment effects earlier and potentially detect those tumours that have a tendency to grow. Nineteen patients with intracranial meningiomas were given irradiation with the 180-MeV proton beam at the Svedberg Laboratory, Uppsala, Sweden. The fractionation schedule used was in general a total dose of 24 Gy in four consecutive daily 6-Gy fractions. Serial 11C-Lmethionine PET examinations were used to evaluate the effect of stereotactic proton beam treatment. The radioactivity uptake in the tumour was evaluated as the ratio to the uptake in normal brain tissue. The follow-up period thus far is 36 months. In 15 of the 19 patients, 11C-L-methionine uptake was reduced 36 months after irradiation compared with the pre-treatment uptake of the tracer. In the total patient group the average reduction was 19.4%. Our results reveal that proton beam irradiation of meningiomas had an inhibitory effect on the methionine uptake in the meningiomas, although tumour size remained unchanged. The combination of unchanged tumour morphology and a reduction in methionine uptake after irradiation suggests that 11C-L-methionine PET might enable earlier evaluation of the treatment effect than is possible with CT or MRI.