High resolution TCSPC imaging of diffuse light with a one-dimensional SPAD array scanning system.

We report a time-correlated single-photon counting (TCSPC) imaging system based on a line-scanning architecture. The system benefits from the high fill-factor, active area, and large dimension of an advanced CMOS single-photon avalanche diode (SPAD) array line-sensor. A two-dimensional image is constructed using a moving mirror to scan the line-sensor field-of-view (FOV) across the target, to enable the efficient acquisition of a two-dimensional 0.26 Mpixel TCSPC image. We demonstrate the capabilities of the system for TCSPC imaging and locating objects obscured in scattering media - specifically to locate a series of discrete point sources of light along an optical fibre submerged in a highly scattering solution. We demonstrate that by selectively imaging using early arriving photons which have undergone less scattering than later arriving photons, our TCSPC imaging system is able to locate the position of discrete point sources of light than a non-time-resolved imaging system.

A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC).

BACKGROUND: We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. CONCLUSIONS: AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC.

A pilot study of indocyanine green clearance as an early predictor of graft function.

Primary graft dysfunction occurs in up to 10% of liver transplant recipients and is the major reason for early mortality and retransplantation. The conventionally used markers of early graft function--i.e., correction of acidosis, glucose requirement, consumption of potassium, serum alanine transaminase (ALT), prothrombin time (PT), bile flow, resolution of encephalopathy and haemodynamic instability can be very misleading as they are dependent on numerous other factors. The aim of this study was to assess the use of indocyanine green clearance (ICG) as a measure of graft function. Peripheral ICG clearance was measured 18-24 hr after liver transplantation in twenty-three consecutive patients (24 transplants). Doppler ultrasonography confirmed normal hepatic arterial blood flow. Correlations between ICG clearance and other markers of graft function and outcome were sought. The mean ICG clearance was 406 mls/min (SD 137.5). A threshold value of 200 ml/min reliably predicted outcome. Significant correlations were found between ICG clearance and times to normalization of PT (P < 0.02) and to the correction of acidosis (P < 0.05). No correlation was found with ALT, PT, bile flow, glucose requirement, or consumption of potassium. ICG clearance measured on the day after liver transplantation accurately reflects graft function and may be used to predict graft survival and final outcome.

Sea blue histiocytosis in a patient with chronic non-neuropathic Niemann-Pick disease.

A patient with Niemann-Pick disease is reported together with family studies. Her liver and bone marrow were shown to be infiltrated with sea blue histiocytes. Other organs, spleen and lung, were presumably also involved but histological proof was not obtained. Enzyme assay of leucocytes, lymphocytes, and cultured skin fibroblasts showed the patient to be deficient in sphingomyelinase activity. In fibroblasts, activity was 5% of normal while for the parents activity was about 50% of normal. The expected partial deficiency was not found using leucocytes or lymphocytes from the parents. Heat stability studies on fresh fibroblast extracts from the propositus indicated that residual sphingomyelinase activity was slightly more labile than that of the controls. It seems clear that chronic Niemann-Pick disease without neurological involvement is associated with sea blue histiocytosis.

Determination of vitamin B 12 absorption by a simple whole body counter.

This paper reports the results of estimating vitamin B(12) absorption by whole body counting in patients without known gastrointestinal disorder, and in patients with pernicious anaemia, idiopathic achlorhydria, achlorhydria following gastric operations, and various forms of small intestinal disease. Patients with pernicious anaemia absorbed less than 30% of the test dose; they could be distinguished from patients without gastrointestinal abnormality and from most achlorhydric patients who secreted more than 300 mg units of intrinsic factor in the post-histamine hour. Nevertheless, the wide range of normal absorption and the variable absorption from the normal gastrointestinal tract is emphasized and discussed. There is no relation between histamine-stimulated intrinsic factor production and vitamin B(12) absorption in patients with small intestinal disease.

Laparoscopy and histology in the diagnosis of chronic liver disease.

We compared laparoscopy with histology in identifying fatty change, fibrosis, the degree of inflammatory activity, cirrhosis and the cause of liver disease. Laparoscopic liver biopsy was performed in 145 consecutive patients. The laparoscopist and the histologist were provided with similar clinical and biochemical information. Both scored the appearances on respective examinations for the degree of fatty change, fibrosis and activity, presence or absence of cirrhosis; and provided a provisional diagnosis. The final diagnosis was determined by clinicopathological conference and clinical follow-up. Laparoscopy was successfully performed in 142 patients (97.9%). Compared with histology, the sensitivity and specificity of laparoscopy for identifying fatty change were 96.4% and 100%, 100% and 95% for fibrosis and 94% and 95% for inflammatory activity, respectively. For cirrhosis, laparoscopy was 100% sensitive and 97.1% specific. Histology missed 10 cases of cirrhosis (6.1%). Histology did, however, provide additional information in 9 patients (6.3%) which contributed to the final diagnosis. Overall, histology is required in addition to laparoscopy in cases where the aetiology is unclear. The sensitivity and specificity in identifying fatty change, fibrosis, activity and cirrhosis are similar for laparoscopy and histology. The combination of information gained on laparoscopy with histology provides the diagnosis in most patients. Laparoscopy may replace the need for liver biopsy in patients in whom the aetiological diagnosis is not in question and the biopsy is being performed to stage the disease. We used it as an integral part of the work-up of a patient with liver disease.

The effect of age on the intravenous sodium glycocholate test.

The clearance of an injected dose of sodium glycocholate has been studied in a group of 23 control subjects who had no evidence of liver disease. A significant correlation was found between bile salt clearance and age. No significant difference was found between the bile salt clearance of male and female subjects. Data derived from a simple compartmental model indicated that decreased clearance of bile salt with age was not specifically related to degenerative changes in hepatocellular integrity, hepatic uptake of bile salts or bile flow.

Primary pulmonary hypertension developing 11 years after a splenorenal shunt for portal hypertension in hepatic cirrhosis.

OBJECTIVE: To describe a patient with pulmonary and portal hypertension and to review the pathogenesis and management of this condition. PATIENT: A 22-year-old woman with portal hypertension and liver cirrhosis who later developed pulmonary hypertension. INTERVENTIONS: The patient received antibiotic therapy and underwent a splenectomy and proximal splenorenal shunt for portal hypertension. She later received hydralazine, digoxin and warfarin for pulmonary hypertension. MAIN OUTCOME MEASURES: After undergoing a splenorenal shunt the patient made a good recovery. However, she later developed pulmonary hypertension and died after undergoing a hysterectomy and a bilateral salpingo-oophorectomy. CONCLUSIONS: The concomitant development of portal and pulmonary hypertension in the same patient has a poor prognosis. The treatment available for patients with these conditions is unsatisfactory and most patients eventually die as a result of cardiovascular disease. Cardiopulmonary and liver transplantation should be considered in suitable patients.

Tubular seminoma. Report of a case.

A 34-year-old man had a 1.5-cm-diameter solid, tan, right testicular tumor. Microscopic examination revealed a predominance of solid tubular structures containing cells with the characteristic features of seminoma cells. The neoplasm, which had a sparse lymphocytic infiltrate, was a rare tubular variant of seminoma, the architecture of which closely resembled that of a Sertoli cell tumor.

The outcome of the first 165 orthotopic liver transplants in Scotland.

The Scottish Liver Transplant Unit is now in its sixth year of existence. We present the outcome of the first 165 transplants which have at least 12 months follow up. The overall patient (n = 143) survival rates at 1, 3 and 5 years were 86.6%, 79.3% and 74.7% and the graft survival rates were 76.9%, 69.1% and 64.8%. The one year survival rate for patients with chronic liver disease (n = 113) was 89.2% compared with 76.6% for acute liver failure (Breslow = 0.05). The one year survival rate for the first 71 patients receiving their primary graft was 81.7% compared with 91.5% for the subsequent 71 patients (Breslow = 0.09). The majority of deaths (n = 29) were due to sepsis (n = 7), at operation (n = 6) or due to graft vascular insufficiency (n = 4). There were two cases of de novo haematological malignancy. The outcome of the first 165 transplants in Scotland compares very well with other countries throughout the world.

Clinical features of alcoholic liver disease.

The severity and range of histological liver lesions caused by alcohol abuse varies considerably; these lesions are not specific for alcoholic damage, and diagnosis of alcoholic liver disease depends on obtaining an adequate history of prolonged alcohol abuse and on excluding other known causes of liver disease. The clinical features of alcoholic liver disease vary greatly and they have been classified into various syndromes. However, the syndromes overlap, the histological features underlying them also overlap and they represent part of a wide clinical spectrum. Alcoholic fatty liver occurs more in younger patients and has a much better prognosis than alcoholic hepatitis or alcoholic cirrhosis, but the previous view that alcoholic fatty liver is an innocuous lesion can no longer be maintained. Alcoholic hepatitis and alcoholic cirrhosis cause more severe syndromes and more florid clinical features, and mortality is related to features of liver failure and variceal bleeding. Abstinence is the only means of ensuring the best possible survival.

Nonlinear polarization coupling and instabilities in single-mode liquid-cored optical fibers.

Polarization coupling is demonstrated in a 0.1-m-long length of nitrobenzene-cored weakly birefringent single-mode optical fiber. Self-switching of the launched mode to the orthogonal polarization is observed at peak powers as low as 1 W. A total phase shift of at least 12pi was induced at a launched peak power of approximately 10 W. To our knowledge, this is the largest phase shift observed experimentally in any nonlinear waveguide at such a low power. The low transmission loss of nitrobenzene makes the device highly attractive for a variety of nonlinear switching applications.