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Biomedical subjects

M Wills

Publications and source records attributed to M Wills.

26 records · Page 2Linked to original sources

Intraoperative urinary cyclic AMP monitoring in primary hyperparathyroidism.

OBJECTIVE: This study examined the utility of intraoperative urinary cyclic 3'5' adenosine monophosphate (UcAMP), an indicator of parathyroid (PTH) hormone end-organ activity, as a "biochemical frozen section," signaling the real-time resolution of PTH hyperactivity during surgery for primary hyperparathyroidism. SUMMARY BACKGROUND DATA: The unsuccessful initial neck exploration for primary hyperparathyroidism, leaving the patient with persistent hyperfunctioning parathyroid tissue, results in part from the surgeon's inability intraoperatively to correlate a gland's gross appearance and size estimation with physiologic function. Preoperative imaging, intraoperative imaging, and intraoperative histologic/cytologic surveillance have not resolved this dilemma. METHODS: Twenty-seven patients underwent a prospective intraoperative UcAMP monitoring protocol. The patients all had a clinical diagnosis of primary hyperparathyroidism and an average preoperative serum calcium of 12.0 +/- 0.3 mg/dl. UcAMP was assayed intraoperatively using 20-minute nonequilibrium radioimmunoassay providing real-time feedback to the operating team. RESULTS: All patients had an elevated UcAMP confirming PTh hyperactivity at the beginning of the procedure. One patient, subsequently found to have an supernumerary ectopic adenoma, had four normal glands identified intraoperatively, and his intraoperative UcAMP values corroborated persistent hyperparathyroidism, the UcAMP of the remaining 26 patients decreased from 7.0 +/- 1.1 to 2.7 +/- 0.7 nm.dl GF (p < .00005) after complete adenoma excision, and they remain normocalcemic. The protocol provided useful and relevant information to the operating team, and aided in surgical decision-making, in 10 of the 27 cases (37%). CONCLUSION: Intraoperative biochemical surveillance with ucAMP monitoring reliably signals resolution of PTH hyperfunction. It is a useful adjunct to the surgeon's skill, judgment, and experience in parathyroid surgery.

Cyclic AMP↗

Reconstitution of Escherichia coli photolyase with flavins and flavin analogues.

Escherichia coli DNA photolyase contains two chromophore cofactors, 1,5-dihydroflavin adenine dinucleotide (FADH2) and (5,10-methenyltetrahydrofolyl)polyglutamate (5,10-MTHF). A procedure was developed for reversible resolution of apophotolyase and its chromophores. To investigate the structures important for the binding of FAD to apophotolyase and of photolyase to DNA, reconstitution experiments with FAD, FMN, riboflavin, 1-deazaFAD, 5-deazaFAD, and F420 were attempted. Only FAD and 5-deazaFAD showed high-affinity binding to apophotolyase. The apoenzyme had no affinity to DNA but did regain its specific binding to thymine dimer containing DNA upon binding stoichiometrically to FAD or 5-deazaFAD. Successful reduction of enzyme-bound FAD with dithionite resulted in complete recovery of photocatalytic activity.

Apoenzymes↗

Passive body heating and sleep: influence of proximity to sleep.

Previous studies have found enhanced delta sleep following body heating. This study assessed the influence of body heating as a function of its proximity to sleep. Electroencephalogram (EEG) sleep patterns were compared following body heating (1 h immersion in water at 41 degrees C) at each of four times of day: morning (MO), afternoon (AF), early evening (EE), and late evening (LE), ending just prior to sleep. A delta filter/integrator system provided objective measures of delta content. Relative to baseline nights, whole-night delta sleep was increased by the two evening heating sessions only, particularly LE heating. Following LE, the increased delta occurred primarily in the first sleep cycle, whereas EE heating elicited increased delta distributed across the later sleep cycles (cycles 2-4). Effects on manually staged indices of slow wave sleep (SWS) were confined to increases in Stage 4 in the first sleep cycle following LE heating. Heating just prior to sleep also resulted in a substantial reduction in the duration of the first rapid eye movement sleep period. Sleep onset time was reduced by heating, particularly EE heating. The results indicate that body heating induces temporary changes that affect sleep propensity and both the quantity and temporal distribution of delta activity in the sleep EEG.

Adult↗

Aging and cholinergic responses in bovine trachealis muscle.

1. The relative potencies of muscarinic agonists on bovine tracheal smooth muscle were unchanged as a consequence of aging and were carbachol greater than oxotremorine greater than muscarine greater than pilocarpine greater than McNeil A-343. 2. During aging, the potencies of carbachol, oxotremorine, McNeil A-343 and pilocarpine, but not muscarine, were reduced. 3. Maximal induced tensions to all the agents studied were reduced as a consequence of age. 4. Irreversible antagonism with benzilylcholine mustard showed that agonist efficacy was significantly reduced during aging. 5. Estimated receptor occupancy at the EC50 was significantly greater in tracheal tissues from the mature versus immature cows for every agonist studied. 6. The dissociation constants for full agonists (carbachol, oxotremorine and methacholine) were decreased with maturation while the converse was observed with partial agonists (McNeil A-343, pilocarpine). 7. We conclude that there are significant changes in the properties and coupling of muscarinic receptors during aging. These changes may contribute to the reduced airway reactivity seen in vivo.

Aging↗

The response of kidney to ionizing radiation combined with hyperthermia induced by ultrasound.

Mouse kidneys were made hyperthermic (42.5 degrees C for 30 min) one hour before, during, or one hour after local irradiation to determine the effect of hyperthermia on radiation damage. An ultrasound beam was used to induce hyperthermia. The urinary concentrations of total protein and albumin were used as criteria of kidney injury. Hyperthermia alone did not induce proteinuria. Radiation alone produced proteinuria that was not correlated with dose. Hyperthermia induced during or after irradiation resulted in a thermal enhancement factor of 1.29 +/- .33. Hyperthermia induced one hour before irradiation resulted in a thermal enhancement factor of 0.88 +/- .05, indicating a radioprotective effect. To the authors' knowledge, this is the first time such an effect has been shown.

Albuminuria↗

Leukocyte and bacterial interrelationships in experimental meningitis.

Eighty-one rabbits were inoculated with known concentrations of type III pneumococci by cisternal puncture and then started on antibiotic therapy the following day. Aliquots of cerebrospinal fluid were sampled at regular intervals both before and after therapy and then analyzed for bacterial titer and leukocyte count. These data were used to examine the interrelationships of inoculum size, leukocyte count, and bacterial titer to each other and their effects both univariately and multivariately on outcome. Inoculum size was the most important single variable affecting outcome, followed in order by the pretherapeutic bacterial titer and leukocyte count. Higher leukocyte counts early in the course of the disease prior to therapy were associated with a favorable outcome. Continued leukocyte elevation after therapy was associated with a poor prognosis. No correlations were found between inoculum size and subsequent bacterial titers; however, the bacterial titer immediately prior to therapy correlated negatively with the level of the early white cell response. The best prognostic information was obtained from the multivariate analysis of inoculum size and pretherapeutic white cell response.

Animals↗

Sensitivity of flavoprotein fluorescence to oxidative state in single isolated heart cells.

The contribution of flavoprotein fluorescence to redox sensitive cellular autofluorescence was studied in single isolated adult rat heart cells. Fluorescence was measured quantitatively under conditions stimulating flavoprotein fluorescence in cells subjected to no inhibitors (sham), to cyanide, to 2,4-dinitrophenol, and to hypoxia. It was found that fluorescence apparently due to flavoproteins could be measured in single cells, and the fluorescence was sensitive to the redox state of the cell. Comparison with NADH fluorescence from single cells indicated that, while flavoprotein fluorescence was less intense, excitation of flavoproteins caused less bleaching of fluorescence when compared to the effect of excitation on NADH fluorescence.

2,4-Dinitrophenol↗