Development of a novel large bandwidth front-end system for high peak power OPCPA systems.

We present the development of a laser system capable of generating bandwidths sufficient to support a sub 30 fs pulse at 910 nm. These pulses have been amplified to 500 mJ of energy at 2 Hz in two stages. The contrast measurements show that the initial seed is clean and suggests that the close in contrast is limited by the evaluation stretcher and compressor. Such a system is suitable for seeding high energy high power OPCPA systems based on KD*P.

Relationship between weight, levodopa and dyskinesia: the significance of levodopa dose per kilogram body weight.

PURPOSE: Levodopa dose per kilogram body weight is reported to be a significant factor for dyskinesia in Parkinson's disease. We have investigated this hypothesis in data from the studies comparing ropinirole versus levodopa as the initial therapy. METHODS: Data from the ropinirole versus levodopa studies 056 and REAL-PET in early Parkinson's disease were pooled and manipulated to calculate levodopa dose per kilogram body weight. Logistic regression analysis was performed to investigate significant variables for the development of dyskinesia. Only the patients on levodopa monotherapy or with ropinirole were analyzed. RESULTS: Analysis of levodopa therapy patients revealed that dyskinetic patients had received significantly higher absolute levodopa dose and levodopa dose per kilogram body weight. Logistic regression revealed that the most significant factor was the higher levodopa dose per kilogram body weight, P = 0.005, odds ratio 1.078, 95% CI 1.023-1.135; younger age was the second factor -P = 0.026. Variables of gender, absolute levodopa dose, weight, disease duration and initial motor Unified Parkinson's disease rating score were not significant. CONCLUSION: Higher levodopa dose per kilogram body weight is an independently significant factor for developing dyskinesia. This relationship should be considered in treatment of Parkinson's disease patients aiming to prevent and manage dyskinesia.

The effect of cimetidine on immunological parameters in Crohn's disease: a double blind trial.

Thirty-six patients with Crohn's disease were entered into a double-blind trial to assess any beneficial effect that cimetidine might have on immunological and clinical status. Eighteen patients were randomized to receive cimetidine, 1 g orally for 28 days, and the other 18 patients to receive a placebo. There was no alteration in clinical status in the cimetidine-treated group. Although 64% of the patients were anergic, augmentation of skin tests to candida, mumps, tuberculin, streptokinase/streptodornase and trichophyton antigens, was not observed in the cimetidine-treated patients. The patients with Crohn's disease, as a whole had higher absolute numbers of suppressor T-lymphocytes, 0.70 X 10(9)/litre (0.21-2.36, n = 35) compared to control values, 0.5 X 10(9)/litre (0.16-1.55, n = 25) (P less than 0.05). However, there was no significant difference in proportions of suppressor and helper T-lymphocytes, lymphocyte activation and humoral immunity after cimetidine treatment. The lack of any clear modulation of immunity by cimetidine, would be against trying H2 antagonists in a long term clinical trial.

Severe selective IgM deficiency.

Among the primary antibody deficiency syndromes, severe selective IgM deficiency (also previously known as type V dysgammaglobulinaemia) is rare, and the majority of previous reports have indicated a fatal outcome. Three adult patients who were found to have a persistently low serum IgM are described. This deficiency was not obviously related to their presenting illness; in two of the patients, who were investigated in detail, it appeared to be of no immediate consequence.

Significance of serum complement levels in patients with gastrointestinal disease.

Levels of the serum complement components, C3 and C4, in patients with Crohn's disease, ulcerative colitis, and miscellaneous gastrointestinal disorders were compared with those of normal blood donors. Significant increases of both components were found in all three patient groups, the highest being in patients with Crohn's disease. Generally, levels of C3 and C4 were lower in patients with inactive rather than active Crohn's disease and ulcerative colitis. These results provide some evidence in support of an immunological basis for inflammatory bowel disease. However, in view of the frequent elevation of C3 and C4 in other gastrointestinal diseases, it is equally possible that the complement components are behaving as acute phase proteins.

IgG myeloma presenting as ulcerative colitis.

Two patients who presented with ulcerative colitis are described. Both were found to have evidence of IgG monoclonal gammopathy and Bence-Jones proteinuria. This association has been reported previously only in the presence of myelomatous infiltration of the gastrointestinal tract or in amyloidosis, and hence the cases reported appear to be unique.

One-hour serum xylose as an absorption test in the tropics.

The 1-hour serum xylose (surface area corrected) as an indication of xylose absorption after 5 g oral D-xylose has been compared with the 5-hour urine excretion test in a tropical population. The study confirmed that the peak serum xylose concentration occurs at 1 hour and that correction to a constant body surface are improves the discrimination between subjects with normal and impaired xylose absorption. The significantly lower reference range for the 1-hour surface area corrected serum xylose (0.55-1.11 mmol/l) compared to the UK figure reflects the reduced absorptive capacity of the jejunum, a result of tropical enteropathy. In view of the difficulties in obtaining accurate urine collections in tropical countries, especially in field studies, it is recommended that the 1-hour serum xylose (surface area corrected) should be adopted as the standard test of xylose absorption.

Reassessment of faecal alpha-1-antitrypsin excretion for use as screening test for intestinal protein loss.

Faecal alpha-1-antitrypsin and 51Cr-albumin losses in 42 patients with either gastrointestinal or hepatic disease were compared. The reference range was derived from measurements in 20 controls without gastrointestinal disease. Alpha-1-antitrypsin excretion was increased in patients with excessive 51Cr-albumin loss, and correlations were found between alpha-1-antitrypsin clearance and 51Cr-albumin excretion. Because of the considerable overlap of faecal alpha-1-antitrypsin excretion between controls and patients, sensitivity and specificity of the test were only 58% and 80%, respectively. This poor reliability could not be explained by sampling error or temporal variations in alpha-1-antitrypsin excretion. These results show that although faecal alpha-1-antitrypsin excretion correlates with 51Cr-albumin excretion when whole groups of patients are studied, its poor sensitivity makes it an unreliable measure of enteric protein loss.

Predicting enteric fever without bacteriological culture results.

We used Bayes' theorem to calculate the probability of enteric fever in 260 patients presenting with undiagnosed fever, without recourse to blood or stool culture results. These individuals were divided into 110 patients with enteric fever (63 culture positive, 47 culture negative) and 150 patients with other causes of fever. Comparison of the frequencies of occurrence of 19 clinical and laboratory events, said to be helpful in the diagnosis of enteric fever, in the two groups revealed that only 8 events were significantly more frequent in enteric fever. These were: a positive Widal test at a screening dilution of 1:40; a peak temperature greater than = 39 degrees C; previous treatment for the fever; a white blood cell count less than 9 X 10(6)/litre; a polymorphonuclear leucocyte count less than 3.5 X 10(6)/litre; splenomegaly; fever duration greater than 7 d; and hepatomegaly. When the probability of enteric fever was determined prospectively in 110 patients, using only 6 of these discriminating events, the probability of patients with a positive prediction having enteric fever (diagnostic specificity) was 0.80 (95% confidence interval: 0.68 to 0.91) and the probability of those with a negative prediction not having enteric fever (diagnostic sensitivity) was 0.92 (0.85 to 0.99). Using all 19 events did not alter the diagnostic specificity or diagnostic sensitivity. This study shows that a small number of clinical and laboratory features can objectively discriminate enteric fever from other causes of fever in the majority of patients. Calculating the probability of enteric fever can aid in diagnosis, when culturing for salmonella is either unavailable or is negative.

Long term role of pergolide as an adjunct therapy in Parkinson's disease: influence on disability, blood pressure, weight and levodopa syndrome.

Pergolide is a dopamine agonist acting on D1 and D2 receptors and has been used as an adjunct therapy with levodopa. We have retrospectively investigated its role over a duration of upto six years in Parkinson's disease (PD) patients to study: (1) its influence on the progression of disability related to PD; (2) effect on blood pressure and weight during the treatment period; (3) whether the use of pergolide has a long term levodopa sparing effect; (4) and how is it tolerated during this period? We studied 43 patients who had been on adjunct therapy with pergolide in addition to levodopa for more than six months. Mean age was 66 years, mean duration of PD prior to adding pergolide was 8 years and final assessment was done after a mean duration of adjunct therapy of 29 (6-72) months. There was no progression of disease disability as assessed on Hoehn and Yahr stage (p=0.09) and Webster score (p=0.20), while there was an improvement in symptom score (p=0.001). There was an insignificant reduction in the dose of levodopa at final assessment from 630 to 535mg (p=0.06). A significant number of patients were able to discontinue taking selegiline (p=0.002). There was no change in the number of patients with hallucinations (p=0.15) and dyskinesia (p=0.09). There was a significant fall in weight (p=0.02), systolic (p=0.023) and diastolic blood pressure (p=0.03). This fall did not correlate with age, dose of pergolide or levodopa or disease severity but was influenced by duration of treatment. Ten patients discontinued pergolide for minor reasons after a mean duration of therapy for 23 months. We conclude that pergolide is a valuable adjunct therapy with levodopa over a duration of upto six years to maintain control of motor symptoms of Parkinson's disease.

Diagnosing enteric fever: a reappraisal.

The diagnostic value of 19 clinical and laboratory events was assessed in 150 enteric fever cases. A logistic regression analysis revealed only 8 predicitive variables for the presence or absence of enteric fever. These were, in order of importance, the white blood cell count, the S. typhi H agglutinin titre, body temperature, the S. typhi O agglutinin titre, the S. paratyphi A H agglutinin titre, the S. paratyphi B H agglutinin titre, age and the fever pattern. This study showed that objective variables like the Widal titres were useful in predicting enteric fever, whilst symptoms such as abdominal pain were unhelpful. Use of all 8 variables to calculate the probability of enteric fever might provide an accurate method of diagnosing or confirming enteric fever when culture results are unavailable or negative.

Studies of the pH gradient across gastric mucus.

We studied the possibility that gastric mucosa protects itself from luminal acid by maintaining a neutral zone adjacent to the mucosa. In the anaesthetised rat pedicles of gastric fundus mucosa with an intact mucus layer were studied. Using pH sensitive antimony chloride microelectrodes, we demonstrated a maximal pH adjacent to the mucosa of 6.68 when luminal pH was 2 (n = 30). The intramucus pH was compromised when luminal acidity was greater than pH 1.5. Addition of 10 mM aspirin or 5% N-acetyl cysteine to the luminal solution also caused a fall in intramucus pH. Sodium taurocholate (10 mM) caused a physical change in the appearance of the mucus which became brittle and fragmented. The pH within the mucus layer fell as a result of this fragmentation. 16, 16 dimethyl prostaglandin E2 prevented the fall in intramucus pH produced by 20 mM aspirin. Similar results were obtained in specimens of human gastric mucosa removed at gastrectomy. These observations suggest that an alkaline zone is maintained within the mucus layer adjacent to the gastric epithelium which may have an important protective role.

Optical parametric chirped-pulse amplification source suitable for seeding high-energy systems.

A short-pulse source based on optical parametric chirped-pulse amplification (OPCPA) technology has been developed with properties that make it a suitable seed for a high-energy OPCPA system. This source generated a diffraction-limited pulse at 910 nm with a full bandwidth of > 165 nm and a spectrum having a transform-limited pulse duration of less than 15 fs. The technique has potential for generating bandwidths > 200 nm and pulse durations < 10 fs.