Intravenous boluses and continuous infusions of L-dopa methyl ester in fluctuating patients with Parkinson's disease.

In six patients with Parkinson's disease exhibiting severe "on-off" phenomena, a 200-mg intravenous bolus of either L-DOPA or of its methyl ester were equally effective in reversing motor deficits, although the duration of action of the methyl ester was shorter. There were no marked differences in pharmacokinetic parameters for L-DOPA plasma levels after administration of L-DOPA and the methyl ester. In three patients, optimal infusion rates for the maintenance of mobility were established for L-DOPA and L-DOPA methyl ester. Both drugs were able to maintain patients "on" throughout a 12-h infusion period. However, on average the optimal infusion rate of L-DOPA methyl ester was 2.7 times greater than that for L-DOPA. There was no marked difference in the plasma levels of L-DOPA achieved, but 3-O-methyl DOPA levels increased more after infusion of L-DOPA methyl ester than after infusion of L-DOPA itself. The half-life of elimination and volume of distribution of L-DOPA formed from the methyl ester were markedly increased compared with values obtained after either an intravenous bolus of methyl ester or after an intravenous infusion of L-DOPA itself. An intravenous bolus of L-DOPA methyl ester produces an equivalent magnitude of clinical response to the same dose of L-DOPA. However, higher optimal infusion rates of methyl ester than L-DOPA are required to produce continuous effect. The pharmacokinetic handling of L-DOPA methyl ester given by intravenous infusion may differ from that of L-DOPA when given by the same route.     

The clinical efficacy of single morning doses of levodopa methyl ester: dispersible Madopar and Sinemet plus in Parkinson disease.

For many patients with Parkinson disease and levodopa-related motor fluctuations, the latency to onset of action of a single dose of a levodopa preparation may be both long and variable. In an effort to find a more rapidly acting and reliable preparation of levodopa, we therefore studied the efficacy of single doses of an oral solution of 250 mg of levodopa methyl ester (ME) with benserazide, 50 mg and of a molar equivalent dose of dispersible Madopar (DM) (50/200) in 13 patients in the fasting state after overnight drug withdrawal. The response of seven of these patients was compared to that after two Sinemet 25/100. The latency to "on" was equally fast with ME and DM, and significantly faster than after standard Sinemet. The duration of "on" was similar with all three. Because of this more rapid relief of "off" periods, both ME and DM offer a potential clinical advantage over standard preparations of levodopa.     

The clinical efficacy of oral levodopa methyl ester solution in reversing afternoon "off" periods in Parkinson's disease

We compared the efficacy of a single dose of an oral solution of levodopa methyl ester (ME) to that of standard levodopa, in the form of a single dose of Madopar, in reversing afternoon "off" periods in 12 patients with Parkinson's disease (PD). The highly soluble ME solution led to a significantly more rapid reversal of "off" periods. This preparation may therefore convey a clinical advantage in patients experiencing motor fluctuations whilst taking multiple daily dosages of levodopa, particularly in those with long or highly variable latency to the next "on" period.     

Poor technetium-99m-DMSA renal uptake with near normal technetium-99m-DTPA uptake caused by tubulointerstitial renal disease.

We present a patient with tubulointerstitial renal disease and poor renal 99mTc-DMSA uptake. A 99mTc-DTPA scan was normal and the creatinine clearance only minimally decreased. In this case, 99mTc-DMSA uptake did not correlate with "global renal function," but rather with the functioning tubular mass.     

Medigap preferred provider organizations: issues, implications, and early experience

The Health Care Financing Administration is sponsoring the Medicare Physician Preferred Provider Organization (PPO) Demonstration to assess the feasibility and desirability of including a PPO option under Medicare. Two sites are currently operational. At one site, Blue Cross and Blue Shield of Arizona is offering a PPO linked with a medigap insurance plan. This "medigap PPO" and its initial experience are described, and a preliminary assessment of the viability and effectiveness of medigap PPOs nationally is provided. Impediments to the development and effectiveness of medigap PPOs are identified and possible government actions discussed.     

Limitations of the clonal agar assay for the assessment of primary human ovarian tumour biopsies.

114 biopsy specimens from 70 patients with ovarian carcinoma at all stages of disease were submitted for assessment of clonogenic capacity in agar. A highly significant correlation was found between agar clonogenicity and patient survival after biopsy. However, problems related to inherent tumour heterogeneity, quality of sample and tissue disaggregation indicate that this technique may have limited applicability in the routine assessment of patients. Only 41 biopsy specimens (36%) from 31 patients (44.3%) complied with the prerequisite criteria for agar clonogenic assessment, namely: (a) the confirmed presence of malignant cells in the biopsy, (b) the ability to prepare a single-cell suspension, and (c) adequate viable cell numbers for assay. Furthermore, although the dominant patterns of agar clonogenic growth could be identified and correlated with stage of disease, the heterogeneity in both initial clonogenic capacity and "self-renewal" capacity assessed by the ability of primary clones to propagate in liquid culture and reclone in agar was too inconsistent for the assay to be used as a prognostic index for the individual patient.     

Seasonal changes in cyclists' performance. Part I. The British Olympic road race squad.

British Olympic road squad cyclists were monitored during the 1980 racing season to evaluate training for the Moscow Games. Riders demonstrated reductions in body fat index, % body fat and endomorphy (p greater than .05). Graded exercise, using a "Racermate" wind load simulator/racing cycle ergometer system, showed reduced cardiovascular demands to warm-up exercise, and increased cardiovascular index, VO2 maximum, aerobic/anaerobic threshold shifts during maximal exercise (NS), with no changes in gearing, equivalent road speed, absolute/relative power output and leg power. Compared with "non-select" riders demonstrated lower body fat index, % body fat and endomorphy (p greater than .05), higher Hb and PCV % (p greater than .05) and elevated neuroticism and extraversion (p greater than .05). Furthermore, "select" riders demonstrated lower HR and CV index during warm-up exercise (p greater than .05), and elevated CV index, VO2 maximum, aerobic/anerobic thresholds during maximal exercise (p greater than .05), resulting from higher gearing, equivalent road speed and absolute/relative power output (p greater than .05).     

The identification by physiotherapists of the physical problems resulting from a mild traumatic brain injury

In New Zealand, over 9000 people are diagnosed with a traumatic brain injury (TBI) each year, with at least 80% being classified as mild. The cognitive deficits resulting from mild traumatic brain injury (MTBI) have been well documented, but this is not the case for the physical problems. As a result, the physical problems are not well understood and few people with a MTBI are referred for physiotherapy. The aim of this research was to use a modified Delphi Technique to gain consensus amongst physiotherapists working with TBI clients with regard to: (1) The common motor performance problems associated with MTBI; (2) The importance of assessing these motor performance problem; and (3) Whether these motor performance problems should be used in a formal assessment (FA) or included as a screening measure (SM). Following a pilot study to establish face validity and clarity of instructions, a national sample of 52 physiotherapists with a minimum of 1 year's experience working with TBI clients was recruited. In Round 1, 42 physiotherapists listed 424 physical problems which, in their clinical experience, may occur in people with a recent MTBI. A planning committee developed these listed problems into 33 items. In Round 2, these items were then rated by the physiotherapists as to their importance of being included in an assessment. Using 75% consensus criteria, 31 items were deemed as being at least 'important' for inclusion. In Round 3, the physiotherapists were asked whether these items should be used in a FA or used as a SM. Of the 31 items which were retained, seven reached consensus for FA (balance with unstable, reduced or changing base of support; dynamic standing balance; high level balance activities; quality of movement; ballistic activities; gait; proprioception). Five items reached consensus for being used as a SM (attention; behaviour; sport and leisure activities; vocational activities; quality of movement). Consensus of classification was not reached for the remaining 19 items which had previously been identified in Round 2 as being at least 'important' to be assessed. These results form the foundation for the development of an assessment/management protocol for physiotherapists working with adults with MTBI.     

Cell-free 59 kDa immunoreactive integrin-linked kinase: a novel marker for ovarian carcinoma.

PURPOSE: We reported that the expression of integrin-linked kinase (ILK) is up-regulated in ovarian carcinomas and that ovarian cancer cells have high expression of ILK. In this study, we have examined the expression of cell-free 59 kDa immunoreactive (ir)ILK in the serum and peritoneal fluid (PTF) of patients with ovarian cancer and evaluated its potential as a serum biomarker for early-stage screening and for monitoring clinical status of patients after chemotherapy treatment. EXPERIMENTAL DESIGN: Thirty-six serum specimens, including normal (n = 6), benign (n = 6), borderline (n = 4), grade 1 (n = 5), grade 2 (n = 5), and grade 3 (n = 10), were evaluated for the expression of irILK by Western blotting. The expression of irILK was evaluated in PTF (n = 10) and peritoneal washings from women with benign ovarian cysts (n = 4). In addition, tissue-conditioned medium obtained from the cultures of primary ovarian tumors (n = 9) was examined for the presence of irILK. Finally, the potential of serum irILK as a biomarker for ovarian cancer screening was evaluated by comparison with cancer antigen 125 (CA 125) concentrations in cancer patients before and after chemotherapy. RESULTS: irILK expression was present in normal serum and in serum of patients with benign ovarian tumors. irILK expression was 6-9-fold higher in the serum of patients with grade 1, grade 2, and grade 3 ovarian cancer than in the serum of healthy volunteers and patients with benign ovarian tumors (P < 0.01). Enhanced expression of irILK in the serum of ovarian cancer patients correlated with the concentration of CA 125. High expression of irILK was present in all 10 PTF tested. Tissue-conditioned medium prepared from malignant ovarian tumors had 4-fold more irILK expression than conditioned medium obtained from borderline and benign tumors (P < 0.01). irILK expression in serum of cancer patients was reduced to basal normal levels after six cycles of Taxol/carboplatin and was consistent with the change of CA 125 levels before and after chemotherapy. CONCLUSIONS: These data suggest that irILK is an ovarian tumor-associated antigen and implicates its potential not only as a biomarker for early-stage screening but also as a marker for monitoring the clinical condition of patients after treatment.