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Biomedical subjects

H Cramer

Publications and source records attributed to H Cramer.

At least 19 recordsLinked to original sources

CEO summit. The new delivery & financing realities. Part III of III.

In cooperation with McManis Associates Inc., Washington, Hospitals & Health Networks recently convened a summit on the integration of financing and delivery in health care. This installment is the third of a three-part series on lessons learned by those on the front lines of integration activity. The session was designed and facilitated by senior associates at McManis. Among the issues summit participants discussed in the second segment: What level of understanding do purchasers have of the factors that differentiate quality in health care services? Can provider-driven integrated delivery systems compete with insurer-driven ones? And what happens when a large integrated delivery system merges with a dominant insurer, as happened in the Philadelphia market? Can that model be successfully replicated in other markets? In this final segment, participants talk about whether providers' deep connections to their communities will add value in a reformed delivery system; how incentives might be aligned among all the players in integrated networks and organizations; how the concept of community focus might be redefined under systems integration; and the process involved in preparing for constant, accelerated change. The second segment concluded with comments about the assets providers and insurers bring to integrated health systems, and whether the merger experience of Graduate Health System and QCC/Independence Blue Cross could be replicated in other markets or not.

Community-Institutional Relations

CEO summit. The new delivery & financing realities. Part II of III.

In cooperation with McManis Associates Inc., Hospitals & Health Networks recently convened a summit on the integration of financing and delivery in health care. This is the second of a three-part series on lessons learned by those on the front lines of integration activity. The session was designed and facilitated by senior associates at McManis. Among the issues discussed in this second segment. What level of understanding do purchasers have of quality differentiators in health care services? Can provider-driven integrated delivery systems compete with insurer-driven ones? And what happens when, as in the Philadelphia market, a large integrated delivery system merges with a dominant insurer? Can that model be replicated in other markets?

Comprehensive Health Care

CEO summit. The new delivery & financing realities. Part I of III.

In cooperation with McManis Associates Inc., Hospitals & Health Networks recently convened a summit on the integration of financing and delivery of health care. This report is the first of a three-part series on lessons learned by those on the front lines of integration activity. The session was designed and facilitated by senior associates at McManis. Among the issues discussed in this first segment: Is integration necessary to satisfy the demands of health care payers? Is integration the way to cost-containment? How can costs be squeezed out of the system? What relationship will physicians have to hospitals and insurers in integrated systems?

Chief Executive Officers, Hospital

Detection of multiple human papillomavirus types in condylomata acuminata from immunosuppressed patients.

Using the hybrid capture method, condylomata acuminata from healthy patients (controls) and patients with altered cell-mediated immunity were analyzed for multiple human papillomavirus (HPV) DNA: 82.9% and 38.0% of lesions from 41 controls and 21 patients, respectively, were HPV DNA-positive only with probes for low-risk HPV types (P = .00035). Using probes for both low- and high-risk HPV types, 16.3% and 52.3% of lesions from 43 controls and 21 patients, respectively, were positive for both probes (P = .0038). Evidence of multiple HPV types was also found by Southern blot and in situ hybridization studies. The mean HPV copy number detected by either probe did not differ significantly among patient groups. Using sensitive techniques, such as hybrid capture, multiple HPV types, including those associated with genital malignancy, can be detected in condylomata acuminata. Serial biopsies demonstrate the dynamic nature of genital HPV infection and that changes in the predominant HPV types may be reflected in tissue pathology.

Biopsy

Accuracy of fine needle aspiration in the pre-operative diagnosis of thyroid neoplasia.

The aim of this study was to determine the accuracy and clinical utility of fine needle aspiration (FNA) for the preoperative diagnosis of patients presenting with solitary thyroid nodules. Between 1987 and 1991, 317 patients with a thyroid nodule underwent FNA. Surgery was performed on 98 of the patients, and the cytologic findings were correlated with the final histologic diagnoses for these cases. Of the 98 patients operated on, satisfactory aspirates were obtained in 85 patients and classified as either malignant, suspicious for malignancy, or benign. The FNA was correct in predicting malignancy in 29 of 35 nodules (82.9%). With the benign nodules, FNA was correct in 44 of 50 nodules (88%). The overall accuracy of FNA was 85.9%. The accuracy for the combination of FNA and frozen section (FS) was 92.6%. We conclude that both FNA and FS are accurate tests that play a useful role in the pre- and intraoperative diagnostic evaluation of patients presenting with solitary thyroid nodules.

Adenoma

Recovery of substance P and related C-terminal fragments on solid-phase extraction cartridges for subsequent high-performance liquid chromatographic separation and radioimmunoassay.

The recoveries of substance P (SP) and five related peptides were evaluated on different types of solid-phase extraction sorbent. Best results were obtained by use of a C18 silica gel cartridge. Marked differences of extraction yields occurred for the different peptide fragments and, in general, recovery increased with increasing hydrophobicity of the peptide when reversed-phase materials like C18 and C8 cartridges were used. This observation is indicative of a sorption-desorption mechanism by prevailing solvophobic interactions. A similar trend was found when phenylpropyl silica gel (CPhenyl), generally known as a reversed-phase adsorbent of lower hydrophobicity, was used. It was concluded that a substantial participation of analyte-matrix pi-pi interactions has to be taken into account when extraction yields are compared with corresponding values obtained by use of a C8 cartridge. With CN silica gel cartridges, marked differences in extraction yields were obtained by use of acetonitrile or methanol as the organic modifier. As an attempt to explain this observation, conformational effects were assumed for the sorption-desorption behaviour of the peptides on the polar matrix.

Amino Acid Sequence

Analysis of human papillomavirus types in exophytic condylomata acuminata by hybrid capture and Southern blot techniques.

Exophytic condylomata acuminata of the external genitalia of 40 patients were analyzed for human papillomavirus (HPV) DNA by the Southern blot and hybrid capture methods. All lesions were initially analyzed by the Southern blot method by using a mixture of HPV type 6, 11, 16, and 18 whole genomic probes. Southern blots demonstrated characteristic PstI restriction patterns of HPV type 6, 11, or 16 in all but one lesion. HPV 6 subtypes accounted for 28 of 39 HPV-positive lesions. Twenty-seven of these 28 lesions contained HPV type 6a, and 1 lesion contained HPV type 6c. Eight lesions contained HPV type 11 and three contained HPV type 16. Two of the three condylomata acuminata containing HPV type 16 were obtained from solid-organ transplant recipients receiving immunosuppressive medications. The third lesion containing HPV type 16 was a typical exophytic condyloma acuminatum from a woman with previously resected vulvar carcinoma. The hybrid capture assay detected HPV DNAs in all lesions except the Southern blot-negative lesion. Twenty-five lesions were positive for the A probe only (HPV types 6 and 11 and related types). All of these lesions were found to contain HPV type 6 or 11 sequences in the Southern blot assay. The remaining 14 lesions were positive for both the A probe and the B probe (HPV types 16 and 18 and related types). The strongest signal in these 14 lesions by the hybrid capture assay was consistent with the result of the Southern blot assay in all but one case. We conclude that (i) HPV type 6a is the most common type found in these lesions, (ii) HPV type 16 may be present more often in exophytic condylomata acuminata from immunosuppressed individuals, (iii) hybrid capture is a useful tool for documenting the presence of HPV sequences in DNAs from exophytic condylomata acuminata, and (iv) in samples containing multiple HPV types, hybrid capture allows detection of minority HPV types.

Blotting, Southern

Medullary thyroid carcinoma: prognostic factors.

Medullary thyroid carcinoma is an uncommon cancer of the thyroid gland. It comprises a neuroendocrine tumor of the calcitonin secreting cells. Its level of aggressiveness lies between that of well-differentiated and anaplastic thyroid malignancies. We have undertaken a retrospective study of 18 patients with medullary thyroid carcinoma to evaluate various parameters for their prognostic value. We looked at epidemiologic factors such as stage, age at onset, sex and the heredity of the disease. In addition various immunohistochemical stains were looked at including Leu-M1, calcitonin, thyroglobulin, somatostatin, carcinoembryonic antigen, neuron specific enolase and BRST-1. Finally, DNA ploidy was determined using the flow cytometer. Stage, age at onset, DNA ploidy and staining for BRST-1 were found to be significant factors in determining outcome of this disease.

Adolescent

Peptidergic modulation of G-protein coupled cyclic-AMP accumulation in the rat caudate nucleus.

Somatostatin, substance P, and vasoactive intestinal polypeptide were incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen tissue of the rat in order to examine the effect of the neuropeptides on G-protein coupled adenylate cyclase in vitro. Somatostatin induced an enhancement of cyclic AMP formation in presence of guanine nucleotides and cholera toxin but inhibited pertussis toxin and forskolin enzyme stimulation. Pertussis toxin and cholera toxin also depressed forskolin-induced stimulation as described previously. Somatostatin was able to antagonize these inhibitory effects of both toxins. On the contrary, substance P reduced GTP and cholera toxin stimulated striatal adenylate cyclase, without affecting forskolin activation. In our preparation, VIP did not influence basal adenylate cyclase activity or the stimulation by guanine nucleotides, cholera toxin, and pertussis toxin. VIP potently inhibited the enhancement of cyclic AMP formation by forskolin and completely antagonized the inhibitory effect of cholera toxin on forskolin activation. These results suggest that neuromodulatory effects of somatostatin, substance P, and VIP are mediated by the inhibitory as well as stimulatory guanine nucleotide proteins G-i and G-s coupled to an adenylate cyclase system.

Adenylate Cyclase Toxin

Parkinson's disease and dementia: clinical and neurochemical correlations.

In 38 old aged parkinsonian patients, two major subgroups could be established: one with predominant akinesia, rigidity, postural instability and accompanying cognitive impairment with intellectual deterioration correlated with duration of disease but not with age of onset and another with predominant tremor and relatively intact intellectual functions. The mean somatostatin-like immunoreactivity (SLI) level in the cerebrospinal fluid (CSF) was significantly lower in parkinsonian patients (21.4 +/- 8.1 fmol ml-1) compared to senile control patients (29.5 +/- 9.4 fmol ml-1). In contrast to senile dementia of Alzheimer's type SLI was not correlated with dementia scores but with motor disease progression. Homovanillic acid (HVA) significantly decreased only in patients without L-DOPA treatment. Correlations between SLI, HVA and 5-hydroxyindole acetic acid (5-HIAA) indicate a degeneration of multiple neuronal networks which includes somatostatinergic neurons.

Aged

The potential clinical impact of the fine needle aspiration/flow cytometric diagnosis of malignant lymphoma.

The objective of this study was to determine the potential application of fine needle aspiration (FNA) and flow cytometry (FCM) for the diagnosis of non-Hodgkin's lymphoma (NHL). At our institution, we have used FNA coupled with FCM to accurately diagnose both reactive lymphoid processes and most lymphomas in a prospective series of more than 90 patients. A retrospective review of 266 patients with NHL who were treated at the London (Ont.) Regional Cancer Centre over a five-year period was performed. Two-thirds presented with palpable lymphadenopathy which would have been amenable to FNA. Based upon the results of our prospective study, FNA/FCM could have provided an accurate diagnosis of malignancy for these patients. Furthermore, the subclassification of the lymphomas would have been accurate in 75% of cases. For 25% of patients, including those with T-cell lymphoma, accurate subclassification may have been problematic. Fifty of the 266 patients developed recurrences during the period of study. Ninety per cent of these were at sites amenable to FNA. Furthermore, the cytomorphology could have indicated whether transformation to a higher grade of lymphoma had occurred. Currently, FNA coupled with FCM is an under-utilized diagnostic technique which has great potential for the investigation of patients with both newly diagnosed and recurrent lymphoma.

Adolescent

Marked improvement of a substance P radioimmunoassay by reduction of 125I-labelled [Tyr8]-substance P prepared by the chloramine-T method with mercaptoethanol and subsequent purification by reversed-phase liquid chromatography.

[Tyr8]-substance P was radiolabelled with 125I by the application of the chloramine-T method. Due to the high oxidative potential of the 125I-chloramine-T system the purified reaction product was converted into a derivative, which presumably had been oxidized to the corresponding sulphoxide at Met11. This conversion was shown by reversed-phase high-performance liquid chromatography after consecutive reduction-oxidation experiments of the freshly prepared radiopeptide. The oxidized derivative exhibited only negligible binding to substance P receptors isolated from rat brain homogenates. However, in contrast, it showed marked cross-reaction to the antibody raised in rabbits against synthetic SP(1-11). The variance in the quantification of identical samples was marked, and the measurement of concentrations in the lower pg/ml range was not sensitive enough to determine levels of substance P-like immunoreactivity in human cerebrospinal fluid. Assay sensitivity could be substantially improved and variance significantly decreased by the use of a radiopeptide, which had been labelled by the chloramine-T method and which had been subsequently reduced with mercaptoethanol and purified by liquid chromatography.

Chloramines

Substance P-like immunoreactivity and somatostatin-like immunoreactivity in the ventricular fluid of patients with chronic pain syndromes.

Substance P-like and somatostatin-like immunoreactivities (SPLI and SLI) were determined in ventricular fluid of patients with chronic pain syndromes and in a comparison group with multiple sclerosis, essential tremor, epilepsy and postanoxic myoclonus. Concentrations of SPLI and SLI were non-significantly decreased by 40% and 33% in chronic pain patients as compared with control patients without pain. There were no differences apparent between subgroups of pain patients (deafferentation pain, neoplasia-induced pain, thalamic pain). High pressure liquid chromatography combined with radioimmunoassay showed marked heterogeneity of SPLI and SLI.

Adult

Adenosine receptor-coupled adenylate cyclase in the caudate nucleus of the rat brain.

5'-(N-Ethylcarboxamido)adenosine (NECA) and N6-[(R)-(phenylisopropyl)]adenosine (PIA) were incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen tissue of the rat, in order to examine the effect of kainic acid and a 6-hydroxydopamine-induced lesion on adenosine receptor coupled adenylate cyclase in vitro. There was an enhancement of formation of cyclic AMP induced by NECA, that was mediated by A2 adenosine receptors. Phenylisopropyl adenosine also stimulated adenylate cyclase in the striatum, with a maximum increase at 0.1 mM. At smaller concentrations, PIA inhibited the basal activity, which was previously described to be an effect mediated by A1 adenosine receptors. In caudate-putamen tissue from rats receiving a unilateral lesion, induced with kainic acid, basal and maximally NECA- and PIA-stimulated activity of adenylate cyclase was decreased. The maximum stimulatory effects of both substances were also significantly decreased, whereas no change of the inhibitory effect of PIA was observed. After unilateral lesion induced with 6-OHDA, basal and maximally NECA- and PIA-activated adenylate cyclase was increased; however, no inhibitory effect of PIA was seen. These results suggest that A2 adenosine receptor-coupled adenylate cyclase was located on neurones intrinsic to the neostriatum and probably postsynaptic to the dopaminergic input. The A1 adenosine receptors seem to be associated with the nigrostriatal pathway implying a presynaptic localization on dopaminergic afferents. In addition, since after both kainic acid- and 6-OHDA-induced lesions, respectively, in caudate-putamen tissue of the contralateral side, PIA no longer inhibited the activity of adenylate cyclase, contralateral structures also appeared to be involved in the regulation of A1 adenosine receptors.

Adenosine

Ventricular fluid neuropeptides in Parkinson's disease. II. Levels of substance P-like immunoreactivity.

Substance P-like immunoreactivity (SPLI) was determined in cerebrovascular fluid of patients with extrapyramidal motor diseases. Patients with Parkinson's disease (PD) showed a SPLI concentration decreased by 30% compared with patients without extrapyramidal disease. No differences were apparent for patients with dystonia. Fluid obtained from the foramen Monro showed higher SPLI concentrations than fluid from a lateral ventricle, indicating that hypothalamic sources are important for ventricular substance P. Lateral ventricular SPLI was particularly low in parkinsonian patients which raises the possibility of a decreased SPergic activity in basal ganglia occurring in PD.

Adult

Determination of the rate of DNA synthesis of human tumor cells obtained by fine needle aspiration. Comparison of flow cytometry and an immunoperoxidase method for the detection of thymidine analogue incorporation.

Two methods of detecting thymidine analogue incorporation by lymphoma, leukemia and myeloma cells obtained by fine needle aspiration (FNA) are described. In one method, cells which have been incubated with the thymidine analogue iododeoxyuridine (IDURD) were exposed to primary monoclonal anti-IDURD antibody and a fluorescein-labeled linking antibody. The fluorescence of the antibody-labeled cells, which had synthesized DNA and incorporated the analogue, was detected by flow cytometry (FCM). In a second method, the cells that incorporated the analogue were detected on glass slide Cytospin preparations by an immunoperoxidase (IP) technique. The IDURD labeling index (LI), as determined by both FCM and IP staining, was compared to the percentage of cycling (S + G2/M) cells as determined by acridine-orange FCM. The data indicate that the IP method is reliable and correlated strongly with FCM determination of LI, percentage S-phase and lymphoma grade. Given the low cost and wide availability of IP technology, the IP method may be desirable for laboratories wishing to supplement cytology reports with cell cycle data.

Biopsy, Needle