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Accessible summary • A review of the concept of motivational interviewing (MI) encompassing what is MI and the development of MI will be provided. Additionally, focus on the spirit, guiding and philosophical principles of MI will be explored prior to reviewing the specific skills and strategies required to work in a MI manner. • A critical appraisal of the evidence base for MI in the field of alcohol misuse will be provided. • Furthermore, Government health policy and clinical guideline recommendations relating to MI will be highlighted. • Conclusions regarding these links will be drawn upon with potential future research implications identified. Abstract A critical appraisal of the evidence that supports efficacy of the brief intervention, motivational interviewing (MI), within the field of alcohol misuse, was made. In order to undertake this appraisal the author will focus on a review of the concept of MI prior to considering the efficacy for MI within the specific field of alcohol misuse.

This study presents the improvement in the US Navy's operational sea ice forecast systems gained by assimilating high horizontal resolution satellite-derived ice concentration products. Since the late 1980's, the ice forecast systems have assimilated near real-time sea ice concentration derived from the Defense Meteorological Satellite Program (DMSP) Special Sensor Microwave/Imager (SSMI and then SSMIS). The resolution of the satellite-derived product was approximately the same as the previous operational ice forecast system (25 km). As the sea ice forecast model resolution increased over time, the need for higher horizontal resolution observational data grew. In 2013, a new Navy sea ice forecast system (Arctic Cap Nowcast/Forecast System – ACNFS) went into operations with a horizontal resolution of ~3.5 km at the North Pole. A method of blending ice concentration observations from the Advanced Microwave Scanning Radiometer (AMSR2) along with a sea ice mask produced by the National Ice Center (NIC) has been developed resulting in an ice concentration product with very high spatial resolution. In this study, ACNFS was initialized with this newly developed high resolution blended ice concentration product. The daily ice edge locations from model hindcast simulations were compared against independent observed ice edge locations. ACNFS initialized using the high resolution blended ice concentration data product decreased predicted ice edge location error compared to the operational system that only assimilated SSMIS data. A second evaluation assimilating the new blended sea ice concentration product into the pre-operational Navy Global Ocean Forecast System 3.1 also showed a substantial improvement in ice edge location over a system using the SSMIS sea ice concentration product alone. This paper describes the technique used to create the blended sea ice concentration product and the significant improvements to both of the Navy's sea ice forecasting systems.

The utility of current chemotherapeutic regimens in the treatment of AIDS-related Kaposi's sarcoma (AIDS-KS) is often compromised by both limited efficacy and substantial toxicity. Pegylated (Stealth) liposomal doxorubicin hydrochloride (SL-DOX) has been demonstrated specifically to deliver high concentrations of doxorubicin to Kaposi's sarcoma (KS) lesions. This phase II study was performed to evaluate the efficacy and safety of SL-DOX in the treatment of moderate to severe AIDS-KS. Patients were treated biweekly with 10, 20, or 40 mg m-2 SL-DOX. Tumour response was assessed according to AIDS Clinical Trials Groups (ACTG) criteria before each cycle. Best response was determined for 238 patients and was achieved after a mean of 2.3 cycles (range 1-20). Fifteen patients (6.3%) had a complete response to SL-DOX, 177 (74.4%) had a partial response, 44 (18.5%) had stable disease and two (0.8%) had disease progression. SL-DOX was well tolerated: ten patients discontinued therapy because of adverse events, in four cases because of neutropenia. Grade 3 or 4 neutropenia occurred after 281 of 2023 cycles (13.9%) but involved 137 of 240 patients (57.1%) for whom data were available. SL-DOX has substantial activity in AIDS-KS. Best response is typically seen after fewer than three cycles of chemotherapy and in some cases may be prolonged. The most important adverse event is neutropenia, which occurs after a minority of cycles but which may occur in over half of all patients.

NC100100 produces marked vascular enhancement (for over 10 minutes) and better visualization of the normal blood flow in canine prostates. Contrast-enhanced ultrasound imaging in CAI mode (2D as well as 3D) matched the pathological measurements of ablation lesion and CTVS tumor sizes and location well. While free hand 3D CAI provided the best visualization of focal abnormalities, measuring the actual tumor size in this mode was limited by the inherent geometric uncertainties of the reconstruction technique. Ultrasound contrast improves the delineation of lesions as small as 4×5 mm (confirmed by pathology) and enables new lesions to be identified. The latter is clinically very important, since it opens up the possibility of reducing the currently very high rate of blind biopsies performed in prostate studies.2,3,4,5,6

The biodistribution and pharmacokinetics of (111)In-DTPA-labeled pegylated liposomes (IDLPL) were studied in 17 patients with locally advanced cancers. The patients received 65-107 MBq of IDLPL, and nuclear medicine whole body gamma camera imaging was used to study liposome biodistribution. The t(1/2beta) of IDLPL was 76.1 h. Positive tumor images were obtained in 15 of 17 studies (4 of 5 breast, 5 of 5 head and neck, 3 of 4 bronchus, 2 of 2 glioma, and 1 of 1 cervix cancer). The levels of tumor liposome uptake estimated from regions of interest on gamma camera images were approximately 0.5-3.5% of the injected dose at 72 h. The greatest levels of uptake were seen in the patients with head and neck cancers [33.0 +/- 15.8% ID/kg (percentage of injected dose/kg)]. The uptake in the lung tumors was at an intermediate level (18.3 +/- 5.7% ID/kg), and the breast cancers showed relatively low levels of uptake (5.3 +/- 2.6% ID/kg). These liposome uptake values mirrored the estimated tumor volumes of the various tumor types (36.2 +/- 18.0 cm3 for squamous cell cancer of the head and neck, 114.5 +/- 42.0 cm3 for lung tumors, and 234.7 +/- 101.4 cm3 for breast tumors). In addition, significant localization of the liposomes was seen in the tissues of the reticuloendothelial system (liver, spleen, and bone marrow). One patient with extensive mucocutaneous AIDS-related Kaposi sarcoma was also studied according to a modified protocol, and prominent deposition of the radiolabeled liposomes was demonstrated in these lesions. An additional two patients with resectable head and neck cancer received 26 MBq of IDLPL 48 h before undergoing surgical excision of their tumors. Samples of the tumor, adjacent normal mucosa, muscle, fat, skin, and salivary tissue were obtained at operation. The levels of tumor uptake were 8.8 and 15.9% ID/kg, respectively, with tumor uptake exceeding that in normal mucosa by a mean ratio of 2.3:1, in skin by 3.6:1, in salivary gland by 5.6:1, in muscle by 8.3:1, and in fat by 10.8:1. These data strongly support the development of pegylated liposomal agents for the treatment of solid tumors, particularly those of the head and neck.

Concomitant chemotherapy and radiotherapy (CCRT) has recently been shown to improve treatment outcome in a range of solid tumors. Pegylated liposomes have the potential to target drugs directly to tumors and may increase the efficacy and reduce the toxicity of CCRT by selectively delivering radiosensitizing agents to tumor, as opposed to normal, tissues. In these studies, we have assessed CCRT using pegylated liposome encapsulated doxorubicin (PLED) and pegylated liposome encapsulated cisplatin (PLEC) against KB head and neck cancer xenograft tumors in nude mice. The addition of low-dose (2 mg/kg) PLED (P0.001) and PLEC (P0.001) significantly increased the effect of 4.5 Gy, but not 9 Gy, single-fraction radiotherapy (SFRT). Both PLED and PLEC were significantly more effective than their unencapsulated counterparts in increasing the effect of SFRT. In addition, PLED (P0.001) and PLEC (P0.05) significantly increased the effect of fractionated radiotherapy (9 Gy in 3 fractions) in two different dosing schedules (2 mg/kg single dose or three sequential doses of 0.67 mg/kg). Unencapsulated diethylenetriaminepentaacetic acid and pegylated liposomal diethylenetriaminepentaacetic acid were used as controls to test the effect of the liposome vehicle and showed no interaction with 4.5 Gy or 9 Gy SFRT (P0.1). CCRT was well-tolerated, with no evidence of increased local or systemic toxicity, as compared with radiotherapy alone. This study is the first to demonstrate the value of pegylated liposomes as vehicles for the delivery of radiosensitizing drugs in CCRT strategies.

The potential value of intratumoral or s.c. injections of pegylated liposomes as locoregionally targeted therapy of tumors and their draining lymph nodes was assessed in nude mice as part of an ongoing program aimed at developing pegylated liposomal radiosensitizers for the treatment of head and neck cancers. Animals received (111)In-labeled diethylenetriaminepentaacetic acid (DTPA), either encapsulated in pegylated liposomes (IDLPL) or in the unencapsulated form ((111)In-DTPA), as intratumoral or s.c. injections, and the local retention, locoregional nodal drainage, and systemic biodistribution were measured. After intratumoral injections, IDLPL were effectively retained in the tumor with an area under the curve (AUC) between 1 and 96 h of 2,574.4% injected dose per gram hours (%ID/g x h). The corresponding value for (111)In-DTPA was 204.4%ID/g x h. Accumulation of IDLPL was seen in ipsilateral lymph nodes. The maximal ipsilateral:contralateral node ratios were 8:1 (2.2 versus 0.27%ID/g) for inguinal nodes at 24 h and 19:1 (2.5 versus 0.13%ID/g) for axillary nodes at 48 h. Unencapsulated (111)In-DTPA showed no evidence of accumulation in locoregional nodes. After s.c. injection, IDLPL were cleared slowly from the injection site with an AUC between 1 and 192 h of 24,051.1%ID/g x h. Unencapsulated (111)In-DTPA was cleared rapidly with an AUC between 1 and 192 h of 46.4%ID/g x h. Again, significant levels of IDLPL were detected in the ipsilateral locoregional nodes, with ipsilateral:contralateral ratios of 121:1 (57.9 versus 0.48%ID/g) at 24 h (inguinal nodes) and 17:1 (5.2 versus 0.3%ID/g) at 72 h (axillary nodes). There was no retention of unencapsulated (111)In-DTPA in the draining nodes. Locoregional administration of pegylated liposomal radiosensitizers may be a useful approach for targeted therapy of head and neck tumors and their nodal metastases.

Lhermitte's sign is an uncommon sequel of radiotherapy to the cervical spinal cord. Although the exact mechanism underlying its occurrence remains unclear; it is felt to be the result of a temporary interference with the turnover and synthesis of myelin, leading to focal demyelination. We have undertaken a detailed analysis of the radiation delivered to four patients who developed the sign after irradiation for malignancies of the head and neck. Our data support the view that radiation dose is crucial to its development, but calculations using the linear-quadratic radiobiological model raise interesting questions regarding the dose-response relationship. In particular, we find that calculations of biologically effective doses are predictive of a late rather than an early normal tissue response. The onset of symptoms after irradiation was apparent in all four patients within 4 months, with resolution in all being complete within a further 6 months. The recognition of this benign transient form of radiation-induced paraesthesia and its differentiation from the later onset, progressive and unremitting symptoms associated with radiation myelopathy is essential in reassuring patients undergoing head and neck irradiation.

Sampling error is an inherent problem of prostate biopsy. Consequently the determination of whether a given carcinoma is clinically significant based on biopsy results is problematic. We assess the dimensions of sampling error and, thereby, provide insight into the potential value of prognostic markers applied to needle biopsies.We constructed 3-dimensional computer models of 21 prostatectomy specimens, including outlines of carcinomas, regions of abnormal E-cadherin expression and individual Gleason patterns. The 6 random systematic core biopsy technique and modifications were simulated using a computer algorithm.In 6 of 21 cases the area of abnormal E-cadherin expression and/or high grade carcinoma was not sampled on 6 random systematic core biopsy. The areas missed were either small or inconsistently under sampled regions of the prostate. Modifying the placement of biopsy needles improved the detection of these features. In addition, percent tumor in the needle appeared to be well correlated to percent tumor in the prostate (r = 0.891, r2 = 0.642).To avoid underestimating the aggressiveness of prostatic carcinoma at least 6 biopsies should be taken from each patient. A more extensive sampling is probably not warranted in all patients but it may prove useful in those in whom extent of disease is unclear or whose general health makes treatment decisions difficult. A reliable estimate of tumor volume in the prostatectomy specimen can be made based on relative amount of tumor in the biopsy specimen on an individual basis.

Vascular tissues from spontaneously hypertensive rats (SHR) exhibit increased nerve growth factor (NGF) levels and increased density of sympathetic innervation compared with those from normotensive Wistar-Kyoto (WKY) rats. The present study asked whether basal NGF secretion or secretion elicited by agents analogous to sympathetic neurotransmitters differ in cultured vascular smooth muscle cells (VSMCs) from SHR and WKY rats. VSMCs were maintained in serum-free medium (SFM) for 72 h and then treated and sampled at 4, 6, 8, and 24 h. Conditioned medium was assayed for NGF using a two-site enzyme-linked immunoassay. NGF secretion by SHR (19.2 +/- 4.6 pg.well-1.48 h-1) and WKY VSMCs (16.7 +/- 5.4 pg.we..-1.48 h-1) was similar in cultures grown in serum-containing medium, whereas SHR VSMCs maintained in SFM secrete more NGF than WKY VSMCs (9.1 +/- 1.9 vs. 2.9 +/- 0.4 pg.well-1.24 h-1, respectively). Treatment of cultures with phenylephrine (0.1-10 microM), neuropeptide Y (1-1,000 nM), or alpha beta-methyleneadenosine 5'-triphosphate (10 and 100 microM) had no effect on NGF secretion by WKY VSMCs, while increasing NGF secretion by SHR VSMCs. Treatment with isoproterenol (0.1-10 microM) decreased NGF secretion by WKY VSMCs but not SHR VSMCs. These data indicate that the regulation of NGF secretion by sympathetic neurotransmitter receptors is different for cultured VSMCs from SHR and WKY rats. If similar differences exist in vivo, they could account for the alterations in NGF levels and sympathetic innervation that are observed.

We propose to use radiolabeled antibodies in combination with external beam radiotherapy to improve locoregional control of head and neck cancer. In this case radiation toxicity to mucosa may become a dose-limiting factor and a calculation of the possible compensatory decrease to the external beam radiotherapy would be needed. For this purpose, the following theoretical phantom of a representative organ of this anatomic region, the larynx, was reconstructed and local dosimetric data were derived for a selection of beta-emitting isotopes. The phantom was reconstructed as cylindrical concentric tubes using the established values of an outer diameter of 38 mm and a height of 44 mm. Published mean adult larynx weight (28 g) and cartilage weight (14.7 g) were used. Mean mucosa weight from 5 mucosa samples of our patients was calculated to be 2.0 +/- 0.4 (SD) g. The remaining weight was apportioned to a fat/muscle compartment (11.3 g). The specific gravity of cartilage (1.10 g/cm3), mucosa (1.04 g/cm3), and fat/muscle (1.04 g/cm3) were used to cross-check the volume/mass disparity of the theoretical tubular tissue shells. The established maximum glottic diameter of 24 mm was used to calculate the central air column volume. Mean laryngeal tumor volume from 8 representative laryngeal tumors was 4.4 +/- 3.1 cm3. Tissue compartment thickness was 660 microns for mucosa, 3100 microns for muscle/fat, and 3320 microns for cartilage. These values allowed the calculation of dose absorbed fractions for a number of theoretical radioimmunoconjugates by extending the established calculation of absorbed fractions for spheres of known diameter to absorbed fractions of tissue planes (annuli) of known thickness. We calculated a Deq for the respective tissues in the larynx for 131I-, 186Re-, 188Re-, 67Cu-, 90Y-, and 153Sm-labeled HMFG1. Compensatory decrease to the external radiotherapy dose is 1.1 Gy for each injection of the radioimmunoconjugate we propose to use (131I-HMFG1). This would be best implemented through the modification of the external radiotherapy fractions falling within 2 effective half-lives of this radioconjugate in the mucosa.

The pharmacokinetics, biodistribution, and dosimetry of an IgG1 radiolabeled anti-mucin mAb (HMFG1) and an isotype-matched control (4D513) were studied in 29 patients with primary head and neck squamous cell carcinoma. Patients were given injections at 3 fixed time points prior to surgery, i.e., 24 (n = 12), 48 (n = 9), or 72 (n = 8) h. They were subsequently classified into two groups based on their immunohistochemical positivity for polymorphic epithelial mucin. Fourteen patients (48%) were positive, 5 of which were studied with both antibodies; and 15 patients were negative (52%), 7 of which were studied with both antibodies. There was no significant difference in serum pharmacokinetics and cumulative urinary clearance of the two antibodies. There was no significant difference in overall normal tissue uptake of specific and control antibody; however, when each component of the normal tissue category was analyzed individually, there was a significantly increased uptake of HMFG1 in mucosa as compared to control antibody. Immunohistochemical studies revealed positive staining of mucosa with HMFG1. There was significantly increased uptake of specific antibody in antigen-positive tumors as compared to uptake of control antibody (P0.02). A tendency for less label loss over time from positive tumors as compared to control was documented. Absolute antibody uptake and tumor/normal tissue ratios demonstrated significant overlap in individual patients from each category depending on the specific ratio (e.g., tumor/adipose tissue) or time point studied; hence arbitrary cutoff values could not be recommended as indicators of specific uptake. Specificity and localization indices were the most reproducible indicators of specific localization. Areas under the curve were calculated for all tissues, and local dosimetry for the two beta-emitting isotopes 131I and 90Y is presented. The Deq values for antigen-positive tumors were 2.9 cGy/mCi for 131I and 9.0 cGy/mCi injected for 90Y. For antigen-negative tumors these values were significantly lower at 0.83 and 2.4 cGy/mCi of 131I and 90Y, respectively. Bone marrow Deq was calculated to be 0.87 cGy/mCi of 131I-HMFG1 injected. Because the purpose of our ongoing research is to assess the therapeutic potential of the combination of radiolabeled antibody and external radiotherapy, detailed dose calculation to local dose-limiting tissues is required. Deq to mucosa was calculated to be 1.1 and 3.8 cGy/mCi of injected 131I and 90Y, respectively. We conclude that a 9-10-Gy dose increment may be achieved in two administrations of 150 mCi of 131I-HMFG1 during a course of external radiotherapy. This may lead to improved control of local disease in patients with head and neck cancer.

A phase 1-2 trial of 90Y-labelled monoclonal antibody, HMFG1 administered intraperitoneally to 30 patients with ovarian carcinoma is presented. The problems encountered with myelotoxicity are described, and the steps which have so far been taken to overcome this and to increase the dose of 90Y to an estimated tumouricidal level. Bone deposition of free 90Y limits the dose which can be administered without severe bone marrow toxicity. The intravenous use of a chelating agent, Ledclair (EDTA) has allowed the dose to be increased from 18 to 30 mCi without causing severe myelotoxicity. 90Y-DTPA MAb is an unstable immunoconjugate in vivo and in vitro. The use of a more stable linkage such as a macrocycle should enable the administered dose to be increased without increasing the amount of free 90Y which becomes available to be deposited in bone. This would be expected to reduce toxicity and increase therapeutic efficacy.

Postnatal ossification of the atlas and axis was studied in Miniature Schnauzers by examining alizarin-stained bone clearings, cleaned dry bones, radiographs, histologic sections, and arterially perfused bone clearings. Sixty-two pups (1 day to 16 weeks old) and 4 adults were examined. In 1-day-old pups, the atlas consisted of 3 separate ossification centers: a left and right neural arch center and midventrally, the intercentrum 1, which formed the body of the atlas. The axis contained 4 separate ossification centers: a left and right neural arch center; centrum 2 in the main part of the axis body; and centrum 1, which formed the caudal part of the dens and the cranial part of the axis body. By 6 weeks of age, the epiphysis on the caudal end of the axis body had begun to ossify. At this time, the intercentrum 2, which developed as a cuboidal ossification center intercalated between centrum 1 and centrum 2 in the middle of the cranial half of the axis body, also began to ossify. The centrum of the proatlas, which formed the apex of the dens, was first seen ossified in a 9-week-old pup. These 10 ossification centers were seen as constant and separate elements. In all dogs, the dens developed from 2 separate ossification centers: the centrum of the proatlas formed the cranial one-quarter, and centrum 1 formed the caudal three-quarters. Dens dysplasia is unlikely to be a result of failure of development of one of the ossification centers for the dens.(ABSTRACT TRUNCATED AT 250 WORDS)

A study is presented on a series of Y-Ba-Cu-O superconductors prepared with the Oxalate Precipitation/Evaporation method. The effect of the preparation conditions on the properties of these superconductors has been studied with X-rays, scanning electron microscopy, Raman spectroscopy, and magnetic measurements. The experiments show that good quality superconductors can be fabricated with this preparation procedure and also indicate that the properties of these materials are very sensitive to the preparation conditions.

A study of splenic function in 28 patients with adult coeliac disease showed no significant correlation between the half life of heat-damaged red cells and either the duration of pre-treatment exposure to gluten or the length of time on a gluten free diet. A significant correlation was found between splenic size and duration of treatment; those patients who had been taking a gluten free diet for the longest time had the smallest spleens. Blood films from 11 of these 28 patients taken before treatment with a gluten free diet were compared with those taken between two and 15 years after the start of treatment. There was no tendency for the hyposplenic changes to regress. In the majority, the changes became more prominent despite strict adherence to the gluten free diet. These findings suggest that splenic atrophy in adult coeliac disease is not reversed by treatment with a gluten free diet and is unlikely to be related to the state of the jejunal mucosa or the duration of initial exposure to gluten.

An automatic circuit recloser has been made available having the features desired for present and future 5kV, 15kV, 25kV and 35kV distribution systems The three phase recloser designated type GIR is designed with a rotating arc interrupter where SF6 gas is used for the interrupter and the insulation. A microprocessor based control unit provides adaptability with presently installed protective devices and is fully adjustable in the field to changing system conditions. The control unit can be interrogated locally or remotely for fault history. Power requirements are so low that the life of the lithium battery is 10 years without the need for a charge circuit. The basic design concepts employed have provided for an increased maintenance interval.

The angular distribution of Sc fragments emitted in the interaction of 400 GeV protons with Ag, La, Lu, and Au has been measured. The distribution for Ag is forward peaked, while that for Lu and Au is sideward peaked, with La being an intermediate case. The implications of this novel transition for the reaction mechanism are considered.

Summary Membrane preparations (1·16 g ml−1 average density) produced by osmotic shock from cotyledonary protein bodies of Phaseolus vulgaris were isolated and purified by sucrose density centrifugation. The constituent polypeptides of these membranes were characteristic and different from those of storage proteins and were shown by SDS gel electrophoresis to consist of, in addition to low mol. wt glycolipid-type material, polypeptides of 16000, 20000, 25000, 30000 and 78000. Of these, the 25000 and the 78000 components appeared to be more tightly associated with the membrane structure than other polypeptides. The 20000, 25000 and 30000 polypeptidea were separated by preparative SDS gel electrophoresis, freed from SDS and extraneous carbohydrates by phenol-borate (pH 8) partitioning and further purified by chromatography on Bio Gel A 5 m in 5 M guanidine HC1. The 30000 polypeptide was identified by chemical, physical and immunochemical methods as a haemagglutinating globulin lectin. The 25000 polypeptide component bore a superficial resemblance to the so-called structural protein generally distributed in a great variety of plants and animal membranes. The 20000 polypeptide has not yet been identified with any known Phaseolus vulgaris protein.

A new technique for measuring changes in the architecture of the small intestinal mucosa is described using a modification of the technique of television image analysis to measure the areas occupied by the surface and crypt epithelium in proximal jejunal biopsies. The ratios of these two areas to each other were then calculated. In 12 control mucosae, the mean ratio (+/-SD) was 2.27 +/- 0.41. In 12 untreated flat mucosae, by contrast, the mean ratio was only 0.24 +/- 0.07. This ten-fold difference, which was highly significant (p0.001), was greater than that for any similar measurements previously reported. This technique is intended for the measurement of changes in the mucosa too small for existing techniques to detect reliably rather than for the diagnosis of coeliac disease.

Summary. The rate of clearance of 15Cr-labelled, heat-damaged red cells from the circulation has been measured in 18 patients with adult coeliac disease. This has been combined with scintillation scanning of the spleen using a colour scanning method. Only two of the patients had clearance times within normal limits. Five had a peripheral blood picture suggestive of splenic atrophy. In these the half time of clearance was greater than 50 min and the scintillation scan showed either no evidence of functioning splenic tissue or only minimal localization of radioactivity suggesting marked hyposplenism. Nine patients had a somewhat prolonged clearance time, the half time of clearance varying between 19 and 44 min. The scan, however, showed an apparently normal spleen and the characteristic changes of splenic atrophy were not present in the peripheral blood film. Two patients had clearance rates faster than that found in control subjects. Both of these patients had enlarged spleens. In one this was associated with hepatic cirrhosis and in the other with an unexplained neutropenia.

Twelve children previously diagnosed as having coeliac disease on criteria now regarded as incomplete have been reinvestigated. Six were found to have an intestinal mucosal lesion characteristic of coeliac disease. All but one had been asymptomatic on a normal diet for more than 18 months. Response to diet fails to distinguish between coeliacs and non-coeliacs. Establishing the diagnosis of coeliac disease by intestinal biopsy is essential, since even apparently symptomless individuals are at considerable risk.

In 39 unselected patients with acute infective hepatitis diagnosed on clinical, epidemiological, and pathological findings, smooth muscle (S.M.) antibody was found in 87% and hepatitis-associated antigen in 33%. The incidence of S.M. antibody was highest during the first month after the onset of symptoms, and the antibody was preponderantly IgM at this stage. S.M. antibody and hepatitis-associated antigen occurred independently, and unlike hepatitis-associated antigen, which was strongly associated with possible parenteral exposure to infection, the incidence of S.M. antibody was not related to the presumed mode of exposure. It is concluded that production of S.M. antibody is more directly related to liver cell damage than to the presence of hepatitis-associated antigen in the serum.

Acute and convalescent sera from 368 patients drawn from a 3-year survey of viral hepatitis in West London were tested for radioimmunoassay for evidence of recent infection with hepatitis A or B and, if neither was found, antibody to Epstein-Barr (EB) virus and cytomegalovirus. In 215 patients (58%) there was evidence of hepatitis A, in 98 (27%) hepatitis B, and in 5 both A and B. 2 patients with evidence of recent EB virus infection were excluded, leaving 48 (13%) attributed to non-A, non-B hepatitis. This illness was milder than hepatitis B as judged by duration of jaundice and peak serum bilirubin alanine-aminotransferase levels. The ratio of men to women was 1.4 to 1, but there was an excess of women in their twenties, most of whom were single. Only one had received blood, and none was a drug addict.

Mouth-caecum transit time (M-CTT) of a lactulose labelled liquid test meal has been measured in 27 coeliac patients and 10 healthy controls using the breath hydrogen technique. Although all patients were urged to maintain a gluten free diet, not all did, and there was, therefore, a wide range in the severity of fat malabsorption within the patient group. Gastric emptying of a 113Indium DTPA-labelled liquid test meal was also assessed in separate studies on six healthy controls and 11 of the coeliac patients. Fasting breath hydrogen concentrations and the response to lactulose, as assessed both by the rate of rise, and the peak breath hydrogen concentration reached, showed no difference between coeliacs and controls, regardless of the presence or absence of steatorrhoea. Mouth-caecum transit time in the 16 coeliac patients with steatorrhea (faecal fat greater than 7 g/24 h) was, however, significantly prolonged being 158 +/- 18 minutes (mean +/- SEM), compared with 70 +/- 9 minutes for the controls (p less than 0.02), and 83 +/- 15 minutes for the 11 coeliacs without steatorrhoea (p less than 0.002). Mouth-caecum transit time in the coeliac patients was linearly related to the 24 hour faecal fat excretion, r = 0.55, n = 27, p less than 0.01. Slow mouth-caecum transit in the coeliacs with steatorrhoea was not caused by delayed gastric emptying as the t1/2 for coeliacs with steatorrhoea was within the normal range. Coeliacs with delayed mouth-caecum transit had impaired insulin release but the postprandial profiles of the other peptides measured (cholecystokinin, GIP, secretin, motilin, neurotensin, enteroglucagon, and peptide YY) were all within the normal range in this group of partially treated coeliac patients.

1. Coeliac patients are known to have an expanded bile salt pool which recirculates slowly due, at least in part, to impaired gall bladder contractility. We have investigated the possibility that delayed small bowel transit of chyme and bile may also contribute to this sluggish recycling. 2. Plasma cholylglycine, total bile acids and cholecystokinin concentrations were measured after a lactulose-labelled test meal whose mouth-caecum transit time (M–C TT) was assessed by the breath hydrogen technique. 3. Overall there were no significant differences in plasma bile acid profiles between seven healthy controls and a group of 25 coeliac patients. However, when subjects were divided according to their M–C TT, the 10 with the slowest transit were found to have significant elevation of fasting levels when compared with the 10 with the fastest transit, fasting total bile acids being 3.4 ± 1.3 versus 0.7 ± 0.6 μmol/l (P < 0.02) and fasting cholylglycine being 0.43 ± 0.17 versus 0.06 ± 0.04 μmol/l (P < 0.05) respectively. 4. Peak bile acid levels did not differ significantly between subjects with fast or slow transit. However, subjects with slow transit were found to have a delay in the return of plasma bile acid levels to fasting levels so that the 4 h postprandial levels were significantly elevated when compared with those observed in the subjects with fast transit (total bile acids 3.6 ± 1.2 versus 0.19 ± 0.1 μmol/l and cholylglycine 0.70 ± 0.13 versus 0.24 ± 0.07 μmol/l respectively, both P < 0.01). 5. We conclude that M–C TT is an important variable determining the postprandial plasma bile acid response, which should be considered when comparing different disease groups in whom gut motility may differ.

During the first 12 months of a total population survey 249 patients were seen with viral hepatitis. A total of 215 of these were tested for hepatitis B antigen (HB Ag) by radioimmunoassay and 32 (15%) were positive. More than five times as many men (27) as women (5) were HBAg positive and 19 of the men were between the ages of 20 and 39 years. There were only four drug addicts among those tested, two of whom were positive, as were two of the four patients who were tattooed. Sixty out of 86 children (under 15 years) were tested for HBAg and none was positive.