Occlusal reconstruction of a collapsed bite by orthodontic treatment, pre-prosthetic surgery and implant supported prostheses. A case report.

The loss of mandibular molars can result in a 'collapsed bite' owing to tilting of teeth adjacent to the gap and overeruption of maxillary molar segments. The lost interarch and interdental space must be regained before prosthetic reconstruction. This case report documents the treatment of a patient by orthodontic, surgical and prosthetic means. The teeth were orthodontically aligned to meet predetermined surgical and prosthetic requirements. The surgical phase comprised a posterior segmental maxillary osteotomy and one-stage placement of three large-diameter implants in the mandible. Finally, the occlusion was restored with mandibular implant-supported prostheses.

Proton magnetic resonance spectroscopy of small regions (1 mL) localized inside superficial human tumors. A clinical feasibility study.

It is demonstrated that the stimulated echo technique for proton magnetic resonance spectroscopy (MRS) can be used to study metabolites in volumes of interest (VOIs) as small as 1 mL localized within superficial human tumors. Access to these small VOIs is important for characterization of tissue regions within a tumor, before, during and after treatment. Spectral appearance resembles that from studies on extracts, and cell suspensions and perfused cells of several tumor types. For the first time proton MRS was used to study cancer treatment in vivo in humans, for a case of radiation treatment of squamous cell carcinoma. No spectral evidence of changed metabolism prior to reduction in tumor size was found. However, after the first period of radiation (39 Gy, 4 weeks), complete disappearance of the metabolite resonances from the spectrum was observed, while a considerable mass still remained, suggesting effective cell destruction upon treatment. Needle aspiration cytology of this mass showed absence of malignant cells, supporting this result.

Regulation of the cytidine phospholipid pathways in human cancer cells and effects of 1-beta-D-arabinofuranosylcytosine: a noninvasive 31P nuclear magnetic resonance study.

Using 31P nuclear magnetic resonance spectroscopy we have noninvasively observed metabolic control through the cytidine pathways of phosphatidylcholine and phosphatidylethanolamine synthesis in intact actively metabolizing MDA-MB-231 human breast cancer cells. Perfusion with the phospholipid precursors ethanolamine or choline (2 mM) indicates that the cytidylyltransferase enzymes are rate limiting for both pathways. Complete inhibition of choline kinase with ethanolamine allowed the observation of the utilization of phosphocholine by the rate-limiting enzyme choline-phosphate cytidylyltransferase. The rate was dependent on the phosphocholine concentration. Inhibition of glycerophosphorylcholine phosphodiesterase with accumulation of substrate was also observed and allows an estimate of the flux through the degradative pathways. The human lymphoma cell line MOLT-4 was also found to contain high levels of phosphocholine and phosphoethanolamine. The levels of these precursors in the MOLT-4 line are lowered by 40% after 6 h when perfused with high dose 1-beta-D-arabinofuranosylcytosine (Ara-C) (400 microns) but are unaffected by 2 microns Ara-C or dideoxycytidine. High dose Ara-C also resulted in lysis in 8-10 h. However, the MDA-MB-231 cell line which is not sensitive to Ara-C showed no change in its spectrum when perfused with Ara-C. A potential mechanism based on classic phospholipid metabolism for the lytic effect of high dose Ara-C is discussed.

Magnetic resonance spectroscopy of tumors and potential in vivo clinical applications: a review.

The development of nuclear magnetic resonance (NMR) spectroscopy as an established research tool for noninvasive studies of cancer cells and for in vivo studies of tumors in animals and humans has led to the possibility that this technique may be used in the future for clinical research studies and monitoring of therapy in cancer patients in combination with magnetic resonance imaging. This article provides a brief qualitative explanation of NMR spectroscopy and then reviews the cell and animal studies detailing which biochemicals can be observed in vivo by 31P, 13C, and 1H NMR. The human studies done to date and their potential for diagnosis and monitoring of therapy are then discussed. In addition, 19F NMR spectroscopic studies of fluorinated drugs and 1H and 31P NMR studies relating to drug resistance are mentioned. The current technical limitations and developing improvements are indicated also.

31P-NMR spectroscopy of human cancer cells proliferating in a basement membrane gel.

We describe a system in which proliferating human breast cancer cells are monitored by NMR spectroscopy for at least 6 days in basement membrane gel (BMG)1 threads. The cells are perfused under standard sterile cell culture conditions. 31P-NMR spectra obtained continuously for up to 64 h showed an increase in the signals owing to an increasing number of cells. Cell division in the BMG is easily observed by microscope or by the human eye as the gel opacifies. Spectra of cells in the BMG threads at 20% confluency show a more rapid signal increase than at 60% confluency. Cells grown in vivo in nude mice show a spectrum markedly similar to in vitro spectra in BMG threads, whereas the same cells in agarose threads lack peaks owing to Pi, glycerophosphocholine, and glycerophosphoethanolamine. With the high resolution obtained from this system we distinguished intracellular from extracellular Pi in vitro, and found that the intracellular pH is equal to that observed in the same cell line in vivo. This cell-BMG system is in effect a model tumor, but it is composed of a homogeneous cell population that can be observed indefinitely as the cells reproduce. The material needed is inexpensive, the technique is simple and efficient, and no adaptation of the spectrometer is required. This model will be useful for studying intracellular metabolism and the interaction of cells with the basement membrane.

A versatile multinuclear probe designed for in vivo NMR spectroscopy: applications to subcutaneous human tumors in mice.

We describe a versatile NMR probe that is designed for a variety of in vivo spectroscopic studies on small animals in vertical wide-bore magnets. Replaceable brackets enable the coils to be exchanged readily in order to observe 1H, 13C, 31P, and other nuclei, and to carry out double-resonance experiments. Two solenoidal coil designs are described and applied to observe 31P, 13C, and 1H natural abundance spectra of subcutaneously implanted human tumors in mice. For 31P and 31C observation with 1H decoupling, a concentric coil arrangement was employed with a broadband inner coil and the outer coil tuned to 1H at 400 MHz. A single coil tuned to 400 MHz was used to observe 1H resonances. A thin copper foil design was found to be superior with respect to S/N and resolution to previously described Faraday shields used to shield the NMR signals originating from nontumor tissues. 31P spectra of in vivo tumor tissue were compared to spectra of in vitro perfused tumor cells of the same origin. Tumor tissue in vivo exhibited much higher levels of inorganic phosphate and phosphocreatine. Signals from [13C2]glucose and its major metabolite, [13C2]lactate, were readily observed and monitored in an unobstructed region of the 13C spectra of tumor tissue in vivo following the injection of [13C2]glucose in adjacent tissues. A 1H spectrum of tumor tissue, characterized by five broad resonances, was observed with excellent water suppression.

Phospholipid metabolism in cancer cells monitored by 31P NMR spectroscopy.

Addition of choline, ethanolamine, or hemicholinium-3 (a choline kinase inhibitor) to the perfusate of human breast cancer cells monitored by 31P NMR spectroscopy resulted in significant changes to phosphomonoester (PME) and phosphodiester (PDE) signals. These results enable us to assign the PMEs to phosphcholine (PC) and phosphoethanolamine (PE), the PDEs to glycerophosphorylcholine and glycerophosphorylethanolamine, and to define the pathways producing them. The PMEs are products of choline and ethanolamine kinases, the first steps in phospholipid synthesis; and the PDEs are substrates of glycerophosphorylcholine phosphodiesterase, the last step in phospholipid catabolism. Furthermore, PC and PE peaks are twice as intense in cells at log phase versus confluency. We also observed these signals in vivo in human colon and breast tumors grown in mice. Since PMEs are low in most nonproliferating tissues, they could form a basis for noninvasive diagnosis. Also, PE and PC are situated between the control enzymes of two major synthetic pathways and will allow noninvasive 31P NMR studies of these pathways in intact cells and in vivo.