Mandibular advancement using an intra-oral osteogenic distraction technique: a report of three clinical cases.

Osteogenic distraction has been used for decades to lengthen limbs and now attention is focused upon its use within the craniofacial skeleton. This paper addresses distraction of the mandible. It is proposed that mandibular osteogenic distraction could be a possible adjunct to the orthodontic treatment of those adult patients with skeletal anomalies, who would benefit from combined orthodontic/orthognathic treatment. Three consecutive cases from one unit are presented, where adult patients with severe Class II division 1 malocclusions have undergone orthodontic treatment combined with mandibular osteogenic distraction, instead of conventional bilateral sagittal split osteotomies.

Impact of dedicated trauma lists on a maxillofacial surgical service.

In 1995, the maxillofacial surgical inpatient services in East Lancashire were centralized in Blackburn Royal Infirmary, and twice-weekly operating lists dedicated to maxillofacial trauma were established. We examined the non-elective workload for three-month periods before and after trauma lists became available to find out the proportion of non-elective operations done out of normal working hours. Although there was an increase in the total number of non-elective patients after centralization, day-time trauma lists allowed a reduction in the proportion of operations performed out of normal working hours. Fewer trauma cases were added to elective lists. Trauma lists allow the unit to comply with the recommendations of both NCEPOD and the Calman report, in that they maximize training opportunities for all staff and facilitate both audit and research.

Growth hormone regulates the distribution of L-type calcium channels in rat adipocyte membranes.

Earlier studies demonstrated that deprivation of growth hormone (GH) for >/=3 h decreased basal and maximally stimulated cytosolic Ca2+ in rat adipocytes and suggested that membrane Ca2+ channels might be decreased. Measurement of L-type Ca2+ channels in purified plasma membranes by immunoassay or dihydropyridine binding indicated a two- to fourfold decrease after 3 h of incubation without GH. No such decrease was seen in unfractionated adipocyte membrane preparations. The decrease in plasma membrane channel content was largely accounted for by redistribution of channels to a light microsomal membrane fraction. Immunoassay of alpha1-, alpha2/delta-, and beta-channel subunits in membrane fractions indicated that the channels redistributed as intact complexes. Addition of GH during the 1st h of incubation prevented channel redistribution, and addition of GH after 3 h restored channel distribution to the GH-replete state of freshly isolated adipocytes. The studies suggest that GH may regulate the abundance of Ca2+ channels in the adipocyte plasma membrane and thereby modulate sensitivity to signals, the expression of which is Ca2+ dependent.

Who decides on the need for antibiotic prophylaxis in patients with major arthroplasties requiring dental treatment: is it a joint responsibility?

The role of antibiotic prophylaxis in patients with prosthetic joints who require dental treatment is controversial. A Working Party of the British Society for Antimicrobial Chemotherapy (BSAC) recently suggested that there was no evidence to support the use of antibiotic prophylaxis in these patients. The purpose of this study was to determine how closely these recommendations were being followed by maxillofacial surgeons (MFS), and to see if there was any consensus on the management of these patients between MFS and orthopaedic surgeons (OPS). With the aid of a postal questionnaire, the opinions of 250 consultant MFS and OPS were sought, response rates were 148 (59.2%) and 113 (41.2%), respectively. Of the OPS, 77.7% always recommended the use of antibiotic prophylaxis as opposed to only 29% of MFS. There were also wide differences in opinion with regard to the antibiotic that should be used in these patients, with the majority of OPS suggesting a cephalosporin, although this may not be the most efficacious antibiotic for oral streptococci. We conclude that this important matter seems to be far from satisfactorily resolved and that further cooperation between the specialties is required to produce guidelines for the safe and effective management of this increasing group of patients.

Alpha 1 and alpha 2 Ca2+ channel subunit expression in human neuronal and small cell carcinoma cells.

Monoclonal antibodies that recognize skeletal muscle dihydropyridine-sensitive calcium channel subunits were used to identify similar proteins in neuronal and small cell carcinoma cell lines. alpha 1-related proteins were detected by FACS analysis on the surface of human neuroblastoma (IMR 32) and small cell carcinoma (DMS 273 and DMS 114) cell lines. alpha 1-like polypeptides from these cells were isolated and partially characterized. The polypeptides exhibit an M(r) similar to that of the L-type channel alpha 1 subunit and are recognized by two distinct anti-alpha 1 mAbs. The data provide biochemical evidence for structural similarities between the alpha 1 subunit of small cell carcinoma and neuronal cell lines. Similarly, an alpha 2-like protein was characterized from these cells. Because alpha 2 is a subunit shared by many subtypes of calcium channels, these data suggest that subunits other than the pore-forming alpha 1 subunit may play an important role in the etiology of Lambert-Eaton syndrome. We demonstrate directly that small cell carcinoma and a cell line derived from peripheral neurons share L-type calcium channel-related proteins and a protein common to many voltage-gated calcium channel subtypes. These data support a model that proposes that cross-reactivity of anti-tumor cell antibodies with presynaptic elements, possibly calcium channels, plays a role in the development of Lambert-Eaton syndrome.

Characterization of muscarinic acetylcholine receptors expressed by an atrial cell line derived from a transgenic mouse tumor.

The properties of muscarinic acetylcholine receptors in the cell line MCM1, derived from an SV40 T-antigen-induced atrial tumor in a transgenic mouse, were determined. Binding studies using the nonselective muscarinic antagonist [3H]quinuclidinyl benzilate, the M1-selective antagonist pirenzepine, and the M2-selective antagonist AFDX-116 indicate that the receptors have the pharmacological properties of the cardiac (M2) receptor subtype. The receptors could be immunoprecipitated with a monoclonal antibody specific for the cardiac receptor, thus confirming the identity of the receptors expressed in these cells. The types of G proteins expressed in the cells were determined by Northern blot analyses: mRNA encoding the alpha subunits of Gs, G(o), and Gi-2, but not Gi-1 or Gi-3, were detected, consistent with previous observations of neonatal mammalian atria. The muscarinic receptors were functionally active, as demonstrated by the ability of the agonist to stimulate phosphoinositide turnover and to inhibit adenylyl cyclase activity. The availability of a mammalian atrial cell line that continues to express the appropriate functionally coupled subtype of muscarinic receptor may provide a useful system for the investigation of the regulation of expression and function of cardiac muscarinic receptors.

Selective regulation of Gi alpha 1 expression and function in PC12 cells by cAMP.

Hormone and neutrotransmitter receptor systems regulate both the activity and expression of GTP-binding proteins (G-proteins). However, relatively little is known about the mechanism by which this regulation occurs. One G-protein subtype, Gi alpha 1, is expressed primarily in neuronal cells. Here, we demonstrate the selective regulation of Gi alpha 1 mRNA and protein levels by cAMP. Treatment of PC12 cells with forskolin increases Gi alpha protein levels. Similarly, incubation of PC12 cells with agents that increase intracellular levels of cAMP, including forskolin, dibutyryl-cAMP, and 8-bromo-cAMP, induce a two- to fourfold increase in Gi alpha 1 mRNA levels. Furthermore, the effect of increased intracellular cAMP is specific for Gi alpha 1 mRNA expression; the levels of mRNA encoding other G-protein subtypes remain unaltered. cAMP-stimulated Gi alpha 1 expression occurs within hours of treatment and is sustained for days. Increasing intracellular cAMP by activation of cell surface adenosine receptors also increases Gi alpha 1 mRNA levels. Treatment of PC12 cells with phorbol esters, NGF, or depolarizing concentrations of KCl did not increase Gi alpha 1 mRNA expression, demonstrating that Gi alpha 1 expression is specifically regulated by cAMP. Guanine nucleotide-mediated inhibition of adenylate cyclase activity was measured in order to determine if the change in Gi alpha protein expression was accompanied by a change in G-protein function. Adenylate cyclase activity in PC12 cells treated with an adenosine analog and therefore expressing higher levels of Gi alpha protein is more sensitive to inhibition by guanine nucleotides than in nontreated PC12 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of the alpha 1 and alpha 2 subunits of the dihydropyridine receptor and ankyrin in skeletal muscle triads.

We have studied the subcellular distribution of the alpha 1 and alpha 2 subunits of the dihydropyridine (DHP) receptor and ankyrin in rat skeletal muscle with immunofluorescence and immunogold labeling techniques. All three proteins were concentrated in the triad junction formed between the T-tubules and sarcoplasmic reticulum. The alpha 1 and alpha 2 subunits of the DHP receptor were colocalized in the junctional T-tubule membrane, supporting their proposed association in a functional complex and the possible participation of the alpha 2 subunit in excitation-contraction coupling. Ankyrin label in the triad showed a distribution different from that of the DHP receptor subunits. In addition, ankyrin was found in longitudinally oriented structures outside the triad. Thus, ankyrin might be involved in organizing the triad and in immobilizing integral membrane proteins in T-tubules and the sarcoplasmic reticulum.

The alpha 1 and alpha 2 polypeptides of the dihydropyridine-sensitive calcium channel differ in developmental expression and tissue distribution.

The dihydropyridine (DHP) binding complex isolated from skeletal muscle contains two large proteins, alpha 1 and alpha 2, and at least two smaller polypeptides. The alpha 1 subunit has a primary structure expected for ion channels and is a functional component of a DHP-sensitive, voltage-activated calcium channel. The functions of the alpha 2 protein and the smaller polypeptides are unknown. We prepared monoclonal antibodies to the alpha 1 and alpha 2 polypeptides and studied the developmental appearance and tissue distribution of these two proteins. In rat skeletal muscle, the levels of alpha 1 are quite low during the first 10 days after birth, then rise dramatically, and, by day 20, approach those found in adult muscle. In direct contrast, alpha 2 is present in substantial amounts in rat muscle at birth and increases only slightly during this same period of development. Furthermore, alpha 1 is detected only in skeletal muscle, whereas alpha 2 is present in a variety of tissues. These results provide evidence for the segregation of these two polypeptides and suggest that the function of alpha 2 is not limited to that associated with the DHP-sensitive calcium channel.

Loss of gelatinase in elicited peritoneal neutrophils of rats.

In previous studies on the respiratory burst of neutrophils, it was observed that the small, water-soluble quinone, duroquinone, activated the respiratory burst in rat peritoneal neutrophils but not in human blood neutrophils. Here we report studies which indicate that a selective diminution of certain granule enzymes, gelatinase and azocaseinase but not elastase, occurs during elicitation in the rat. Neutrophils circulating in rat blood have about twice the amount of gelatinase and azocaseinase activity as compared to elicited peritoneal cells, and the respiratory burst of circulating cells is stimulated to only about 20% by duroquinone. The significance of these results is considered in terms of activation of the neutrophil respiratory burst.

Monoclonal antibody to the alpha 1-subunit of the dihydropyridine-binding complex inhibits calcium currents in BC3H1 myocytes.

A monoclonal antibody, mAb 1A, previously shown to recognize the dihydropyridine (DHP)-binding complex in rabbit muscle transverse tubules, inhibits voltage-sensitive calcium channel activity in a mouse muscle cell line. mAb 1A applied externally to BC3H1 muscle cells produced a concentration-dependent attenuation of the slowly-activating, DHP-sensitive, high-threshold calcium current. mAb 1A had no direct effect on either the rapidly-activating, DHP-insensitive, low-threshold calcium current or the delayed outward potassium current. However, sodium current kinetics were altered. On Western blot analysis of immunoaffinity-purified protein solubilized from BC3H1 membranes, mAb 1A recognized a Mr 210,000 polypeptide that is an analogous to the alpha 1 subunit of the DHP-binding complex from skeletal muscle. These results suggest that an extracellular segment of the alpha 1 subunit of the DHP-binding complex plays a functionally important role in voltage-gated calcium currents.

Excessive bleeding after surgery in osteogenesis imperfecta.

A case is reported of a patient with osteogenesis imperfecta who bled excessively during orthognathic surgery despite normal pre-operative screening. Possible mechanisms for this bleeding are discussed.

Monoclonal antibody identifies a 200-kDa subunit of the dihydropyridine-sensitive calcium channel.

A monoclonal antibody, mAb 1A, that immunoprecipitates the [3H]PN200-110-binding complex from rabbit skeletal muscle has been used to study the subunit structure of the dihydropyridine-sensitive, voltage-activated calcium channel. Digitonin-solubilized [3H]PN200-110-binding component, purified by wheat germ agglutinin chromatography, sediments as a 21 S complex. The sedimentation coefficient of the complex is increased to about 24 S after incubation with mAb 1A IgG. Four polypeptides with apparent molecular weights under nonreducing conditions of 220,000, 200,000, 61,000, and 33,000 co-sediment with the 21 S complex. mAb 1A recognizes the Mr 200,000 polypeptide, as shown by Western blotting analysis. [3H] PN200-110 complex purified by wheat germ agglutinin chromatography followed by immunoaffinity chromatography on an mAb 1A column is comprised primarily of the same four polypeptides. When analyzed by sodium dodecyl sulfate gel electrophoresis under reducing conditions, the Mr 220,000 protein migrates as a polypeptide of Mr 143,000; the mobility of the Mr 200,000 protein recognized by mAb 1A is unaffected by reduction. Thus, the Mr 200,000 polypeptide appears to be a previously undescribed component of the dihydropyridine-binding complex and, in association with the other polypeptides, may comprise the voltage-sensitive calcium channel.

Abnormal expression of surface immunoglobulin isotypes on antigen-binding B lymphocytes from mice tolerant to trinitrophenyl determinants.

Temporary B-cell tolerance to the trinitrophenyl (TNP) hapten can be produced in BDF1 mice by intraperitoneal injection of trinitrobenzene sulfonic acid (TNBS). Antigen-binding cells (ABC) specific to TNP, measured as TNP donkey erythrocyte rosettes, are found in tolerant mice as well as in immune mice. We have studied the surface immunoglobulin isotype profile of these TNP-binding lymphocytes (TNP-ABC) in four groups of animals: nonimmune, immune, tolerant, and tolerant-challenged. Immune mice received intravenous TNP sheep erythrocytes (TNP-SRC), whereas tolerant-challenged mice received TNP-SRC and TNBS on Day 0. TNP-ABC from mice immunized with TNP-SRC exhibit increased expression of surface IgG and decreased expression of surface IgD, compared to the ABC from nonimmune mice. Tolerant mice have a higher proportion of ABC with surface IgG, and a lower proportion with surface IgD, than nonimmune mice. Tolerant-challenged mice have a lower proportion of ABC with surface IgG, and a higher proportion with surface IgD, than immune mice. Thus, B-cell tolerance in this model entails an attenuation of the surface immunoglobulin isotype switch (loss of IgD and gain of IgG) on ABC seen in the normal immune response. For most TNP-ABC, tolerogen exposure prevents the switch in surface isotypes normally induced by exposure to TNP antigen; i.e., the tolerance lesion precedes the surface isotype switch. However, a minority of the TNP-ABC appear to switch surface isotypes in response to the tolerogen itself.

Osteoradionecrosis: a study of the incidence in the North West of England.

A retrospective survey of 200 patients was carried out to determine the incidence of osteoradionecrosis in the North West of England. The patients all had been treated with radiotherapy for squamous cell carcinoma of the oral cavity. An overall incidence of osteoradionecrosis of 19.6% was found. Cases were designated as having major, moderate or minor osteoradionecrosis. The incidence of major osteoradionecrosis was 8%. Hemimandibulectomy was required for management of the necrosis in 3%. Factors involved in the aetiology are discussed.

The management of osteoradionecrosis of the jaws.

Therapeutic measures used in the management of osteoradionecrosis (ORN) of the jaws are reviewed with reference to clinical case material. The development of rational treatment regimes designed to deal with the underlying pathological problem are discussed.

Experimental transcerebral fistula. Perineural olfactory CSF flow in the normal, hydrocephalic, and postoperative hydrocephalic dog shown by radionuclide ventriculography.

Cerebrospinal fluid dynamics were studied in eight dogs during normal, hydrocephalic, and postoperative phases. Radionuclide-labeled substances introduced into the normal ventricular system flow out of the exits from the fourth ventricle to the convexity subarachnoid spaces superiorly to be absorbed in the sagittal sinus, and basorostrally to the exits from the perineural olfactory sheath into the nose to produce physiological cerebrospinal fluid (CSF) rhinorrhea. Serial radionuclide ventriculography of the head following intraventricular isotope injection of labeled proteins and chelate into the kaolin-induced hydrocephalic system shows a high degree of ventricular stasis with no perineural olfactory nerve flow (rhinorrhea). An operative transcerebral fistula, fashioned from a dilated lateral ventricle to the convexity subarachnoid space, reestablishes perineural olfactory flow of CSF into the nose, as demonstrated by the radionuclide ventriculography studies. This suggests a potential method for treatment of hydrocephalus. Serial imaging studies in this surgically modified system clearly demonstrate radionuclide flow through the patent fistula to distal absorption sites, thereby bypassing the basal obstruction. Moreover, augmented CSF pressures associated with obstructive hydrocephalus can be controlled by such treatment. The application of this method in treating clinical hydrocephalus is discussed with emphasis on fistula arachnoid closure to assure fistula patency.