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Biomedical subjects

G L Becker

Publications and source records attributed to G L Becker.

52 records · Page 3Linked to original sources

Calcification mechanisms: roles for cells and mineral.

Recent findings slggest that cellular activity and mineral chemistry have important roles in initiating mineral formation in calcifying tissues. Under biological conditions, hydroxyapatite (HA), the predominant and most stable form of insoluble calcium phosphate, forms only through a more soluble, noncrystalline precursor, amorphous calcium phosphate (ACP). The conversion of ACP to HA can be extensively inhibited by many biologically ubiquitous small ions at their typical tissue concentrations. The earliest mineral deposits in the matrix of several calcifying tissues are associated with tiny membranous vesicles. Intramitochondrial calcium phosphate granules are also seen within intact cells of certain calcifying tissues. Current hypotheses for initial mineral deposition, based on these findings, are reviewed.

Bone and Bones↗

Comparative studies of intra- and extramitochondrial calcium phosphates from the hepatopancreas of the blue crab (Callinectes sapidus).

Subcellular fractions of cytoplasmic mineral granules and mineral-loaded mitochondria were isolated from whole homogenates of hepatopancreas of the blue crab (Callinectes sapidus). Chemical, physical, and morphologic studies were carried out on both subcellular fractions, with and without prior removal of organic components by hydrazine extraction. In contrast to cytoplasmic granules, whole mitochondria contained appreciable amounts of mineral ions not associated with a solid mineral phase. Quantitative analyses and infrared spectroscopy showed cytoplasmic and mitochondrial mineral phases to be calcium phosphates of similar but not identical composition. Both cytoplasmic and mitochondrial mineral phases, as in synthetic amorphous calcium phosphate, show noncrystalline patterns when examined by infrared spectroscopy and x-ray diffraction, and a common ultrastructure of clustered spheres of approximately 100 A diameter. The findings suggest that amorphous calcium phosphate in biological systems may exhibit appreciable variation in Ca/P and in the content of foreign ions such as Mg2+, ADP, and ATP. A mitochondriogenic mechanism of calcification could not be confirmed nor refuted by this study.

Animals↗

Origin, diagnosis, and treatment of the dental manifestations of vitamin D-resistant rickets: review of the literature and report of case.

Previous discussions center on early diagnosis, initial treatment, and follow-up therapy for the patient with vitamin D-resistant rickets. Both the medical and dental aspects of treatment for these patients has a long-range effect on the normal developmental patterns. Although treatment is begun at an early age, some rachitic skeletal effects such as minor bowing of the legs and bossing of the skull will invariably be noticed. In patients with controlled rickets the alveolar processes undergo normal development, with apparent normal dental eruption. The poor development and calcification of the alveolus seen in the untreated patient leads to loss of the lamina dura and periodontal ligament of the teeth. Patients with resistant rickets possess a functional dentition, although not without inherent defects. Various degrees of fracture and attrition of enamel can be seen, and hypoplasia of dentin is nearly a universal result. Defects extending to the dentinoenamel junction have been shown in repeated cases. Cementum, because of its close relationship with dentin calcification, also appears abnormal. Pulp tissue may undergo abberations of physiology in resistant rickets, although further work in this respect is needed. With respect to the possible dental pathoses seen in this disease, the dental history of the patient with resistant rickets discussed in this report showed that several of the deciduous teeth, possibly the mandibular left second premolar and right first molar, and definitely the maxillary right second premolar and canine and the mandibular left canine had all undergone pulpal degeneration of apparently unknown causation. In the maxillary right second premolar and the mandibular left canine, enamel fractures were clinically and radiographically apparent. However, the maxillary right canine originally had an acute abscess with no defects other than normal, minimal wear facets. No causative factor for its necrosis could be found. Overt enamel fractures in the maxillary right second premolar and the mandibular left canine may have led to microexposures of the pulp with subsequent bacterial pulpal contamination. Suppuration present in several of the pulps when first entered during endodontic treatment, as well as chronic fistulas in several areas, support the conclusion that contamination by some means does indeed occur.

Abscess↗

Atomic structure of intracellular amorphous calcium phosphate deposits.

The radial distribution function calculated from x-ray diffraction of mineralized cytoplasmic structures isolated from the hepatopancreas of the blue crab (Callinectes sapidus) is very similar to that previously found for synthetic amorphous calcium phosphate. Both types of mineral apparently have only short-range atomic order, represented as a neutral ion cluster of about 10 A in longest dimension, whose probable composition is expressed by the formula Ca9(PO4)6. The minor differences observed are attributed to the presence in the biological mineral of significant amounts of Mg-2+ and ATP. Synthetic amorphous calcium phosphate in contact with a solution containing an amount of ATP equivalent to that of the biological mineral failed to undergo conversion to the thermodynamically more stable hydroxyapatite. The amorphous calcium phosphate of the cytoplasmic mineral granules is similarly stable, and does not undergo conversion to hydroxyapatite, presumably owing to the presence of ATP and Mg-2+, known in inhibitors of the conversion process. The physiological implications of mineral deposits consisting of stabilized calcium phosphate ion clusters are discussed.

Animals↗

Calcium phosphate granules in the hepatopancreas of the blue crab Callinectes sapidus.

The hepatopancreas of the adult male blue crab Callinectes sapidus in intermolt was found to contain substantial amounts of calcium, magnesium, and inorganic phosphorus, averaging about 260, 20, and 250 microg-atoms per g wet tissue, respectively, accounting for over 10% of the tissue dry weight. Electron microscopy of the intact tissue showed three qualitatively different granular structures having electron densities suggestive of high mineral content. After fractionation of the tissue using centrifugal techniques, almost 95% of the total mineral was found to reside in a heavy, nonmitochondrial particulate fraction(s). The bulk of the low-speed pellet consisted of relatively dense, roughly spherical granules 1-5 microm in diameter, which could be considerably purified by repeated suspension in water and low-speed sedimentation. In the electron microscope the isolated granules appeared basically similar to one of the three characteristic types of electron-dense granules seen in the intact tissue. Although the freshly isolated granules lost approximately 50% of their wet weight when dried at 105 degrees C, only 10% more was lost upon dry ashing at 450 degrees C, suggesting a fairly low content of organic material. Chemical analysis revealed calcium, magnesium, and inorganic phosphate at 5.7, 2.1, and 4.4 microg-atoms per mg dried granules, respectively, accounting for 69% of the dry weight of the fraction. By specific enzymatic assays, the freshly isolated granules were found to contain ATP, ADP, and AMP at levels of 0.13, 0.03, and 0.01 micromol/mg, or 8% of their total dry weight. The remainder of the total phosphorus contributed an additional 3%, whereas carbonate, citrate, oxalate, and protein each constituted no more than 1%. The mineral granules of the crab hepatopancreas appear to function as storage forms of calcium and phosphate during the intermolt period. This tissue appears promising as a model for study of the cellular events associated with biological calcification, since conventional biochemical techniques can be employed. Furthermore, the major mineralized component of the tissue can be obtained in large amounts for direct study by a simple fractionation procedure.

Adenine Nucleotides↗

The effectiveness of oral clonidine as a sedative/anxiolytic and as a drug to blunt the hemodynamic responses to laryngoscopy.

STUDY OBJECTIVE: To determine the effects of oral clonidine premedication on sedative, anxiolytic, and hemodynamic responses during the immediate preoperative period, laryngoscopy/intubation, and postanesthetic recovery. DESIGN: Randomized double-blind assignment to one of four treatment groups (clonidine 0.1 mg, clonidine 0.2 mg, triazolam 0.25 mg, or placebo); n = 10 per group. SETTING: Inpatient surgery in a university-staffed tertiary center. PATIENTS: Forty ASA physical status I and II adults of both sexes scheduled for a variety of procedures requiring general anesthesia. INTERVENTIONS: Anxiety and sedation scored on ordinal scale at time of treatment and 90 minutes later, just prior to anesthetic induction. Standardized induction protocol with automated hemodynamic monitoring at 1-minute intervals and a 45-second laryngoscopy to ensure a vigorous stress response. MEASUREMENTS AND MAIN RESULTS: Triazolam and both doses of clonidine increased sedation at 90 minutes both absolutely and compared with a placebo. Clonidine 0.2 mg decreased anxiety absolutely at 90 minutes but no more than a placebo. Clonidine 0.2 mg decreased systolic, mean, and diastolic blood pressures (BPs) but not heart rate (HR) at 90 minutes. Clonidine 0.2 mg also blunted the increase in systolic blood pressure (SP) [but not in diastolic blood pressure (DP) or HR] that accompanied laryngoscopy. There were no treatment differences in postanesthetic hemodynamics or duration of recovery. CONCLUSIONS: Oral clonidine 0.2 mg was effective in reducing the level of behavioral and hemodynamic responses preoperatively and in blunting systolic hypertension produced by prolonged laryngoscopy.

Adult↗

Atracurium use in a patient with familial periodic paralysis.

We describe a patient with the hypokalemic type of familial periodic paralysis (FPP) who received atracurium for muscle relaxation as required for diagnostic laparoscopy. Electrocardiographic (EKG) T-wave changes suggestive of hypokalemia were not supported by blood determinations. Arterial blood measurements of potassium (K+), pH, and arterial carbon dioxide tension (PaCO2) and the patient's esophageal temperature were maintained within normal limits. The degree of muscle relaxation was closely monitored by a peripheral nerve stimulator and train-of-four (TOF) measurement of muscle twitch height. At the conclusion of the surgical procedure, no reversal to the muscle relaxant was needed or given. The patient regained preoperative muscle strength, and her postoperative course was uneventful.

Adult↗

Anesthesia for glucagonoma resection.

Anesthetic experience with three cases of the resection of glucagonoma, a rare tumor of alpha cells of pancreatic islets, is presented. Marked increases of blood glucagon and glucose levels, with the potential for clinically significant metabolic and myocardial dysfunction, did not occur during anesthesia and surgery. Associated tumors of other endocrine cell types also were absent in the three study patients. Strategies for anticipating and managing other perioperative problems associated with glucagonoma also are discussed.

Adult↗

Oral clonidine blunts the hemodynamic responses to brief but not prolonged laryngoscopy.

STUDY OBJECTIVE: To determine whether a 300 micrograms dose of oral clonidine given 90 minutes prior to laryngoscopy and intubation provides hemodynamic protection from the stress of a brief (15-second) and/or a prolonged (45-second) laryngoscopy. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Inpatients and outpatients scheduled for general anesthesia with intubation at a university-affiliated medical center. PATIENTS: Forty patients who gave informed, written consent to receive either an oral placebo or clonidine 5 micrograms/kg (up to a maximum dose of 300 micrograms) 90 minutes prior to induction of anesthesia and to undergo either brief or prolonged laryngoscopy prior to intubation. INTERVENTIONS: The patients underwent a standardized induction sequence that included d-tubocurarine 3 mg, thiopental sodium 5 mg/kg, and succinylcholine 1.5 mg/kg. The four treatment groups (each n = 10) included (1) placebo with 15-second laryngoscopy, (2) placebo with 45-second laryngoscopy, (3) clonidine with 15-second laryngoscopy, and (4) clonidine with 45-second laryngoscopy. Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were mechanically obtained and recorded at 1-minute intervals for 12 minutes. MEASUREMENTS AND MAIN RESULTS: There were no differences between groups in the premedication hemodynamic measurements. Within each group, maximal hemodynamic variables increased significantly over the corresponding baseline values for that group. In the 15-second, but not the 45-second, laryngoscopy, clonidine successfully blunted the maximum SBP and DBP obtained when compared with the corresponding control group. In both the 15- and 45-second clonidine groups, maximum HR was significantly lower than in the corresponding placebo groups. CONCLUSIONS: Oral clonidine, when used as a preoperative medication, affords hemodynamic protection to patients undergoing a 15-second laryngoscopy. However, the stress of a 45-second laryngoscopy may be too great or the 300 micrograms dose of clonidine too low to provide hemodynamic protection for patients in this group.

Administration, Oral↗

Effects of subcutaneous verapamil on the duration of local anesthetic blockade.

STUDY OBJECTIVES: To determine whether a subcutaneous injection of verapamil will provide local anesthesia and whether a mixture of lidocaine and verapamil will prolong the anesthetic effect of lidocaine alone. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Preanesthetic area of a large metropolitan teaching hospital. PATIENTS: 20 volunteers. INTERVENTIONS: All volunteers received 4 injections of normal saline, verapamil, lidocaine, and lidocaine-verapamil at the volar aspect of the forearm. The sites were tested with a 26-gauge needle to be sure the sensation of sharp could be appreciated. The injections were performed in a randomized, double-blind fashion using a sterile technique. The 4 areas were tested at 1-minute intervals using a 26-gauge needle until the sensation of sharp was again perceived. MEASUREMENTS AND MAIN RESULTS: Injection sites were examined for the presence and degree of erythema. Volunteers were asked to rate the degree of pain felt during and immediately after injection. The time elapsed until the person was again able to perceive sharp from a 26-gauge needle prick was measured at all 4 sites. When compared with the effects of normal saline, subcutaneous verapamil provided local anesthesia to pinprick. The mixture of verapamil and lidocaine also provided anesthesia to pinprick, but the duration of effect was less than that provided by lidocaine alone. The use of verapamil alone and in combination with lidocaine was associated with a marked degree of erythema and edema. CONCLUSIONS: Verapamil injected subcutaneously provides a degree of local anesthesia. However, this effect is hampered by a local reaction at the injection site and a short duration of action. The mixture of lidocaine and verapamil provides a shorter duration of action than does lidocaine alone.

Adult↗