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Biomedical subjects

G R Hoffman

Publications and source records attributed to G R Hoffman.

At least 19 recordsLinked to original sources
PubMed2006

Sternoclavicular joint pseudo-tumour: a case report and literature review.

This case report describes the development of a post-treatment enlargement of the sternoclavicular joint, diagnosed as a pseudo-tumour, in a patient who had previously undergone radical neck dissection and post-operative radiotherapy for metastatic mucoepidermoid carcinoma. Although pseudo-tumour has been previously reported in the surgical literature, it remains an uncommonly recognized condition. We present a review of the literature and discuss the condition's pathogenesis. We also highlight its importance to both the surgeon and the oncologist when considering the differential diagnosis of a swelling in the clavicular region, typically occurring following radical surgery for malignant disease in the neck.

Aged↗
PubMed2006

A prospective study into the demographics and treatment of paediatric facial lacerations.

To evaluate the demographics and treatment of facial lacerations occurring in a paediatric patient cohort. We undertook a prospective study of 106 children who sustained a soft tissue facial injury and who presented to an Accident and Emergency department in a UK district general hospital supporting a population of 750,000. Approximately 31,000 are dependent children between the age of 0-12 years. Our results show that the majority of paediatric patients who sustained a facial laceration were male (62%). The frequency of this injury was greatest amongst males across all age groups. The majority of children above 3 years of age sustained their injury outdoors. The peak time for injury varied for different age groups. The 0-3 year olds sustained the highest incidence of injuries around 17:00 h. A bi-modal time pattern was seen in the 4-6 year age group, initially at 12:00 h with a second peak at 17:00 h. The most frequent aetiology was play. A significant finding was that 8% of the injuries that were managed resulted from a dog bite. Almost 50% of children above 4 years of age, who required primary closure of their laceration, were able to tolerate their treatment being performed under local anaesthesia. The pattern of facial lacerations in our study supports the results of previous studies. Our data has provided further insight into the presentation of these injuries. These studies are valuable in targeted injury prevention programmes aimed at potentially reducing the nature, incidence and severity of facial soft tissue trauma in children in the UK.

Age Distribution↗
PubMed2006

Bilateral axillary metastasis from a primary ethmoidal squamous cell carcinoma.

The development of infra-clavicular lymph node metastasis from head and neck squamous cell carcinoma is an uncommon event. We present a rare case of bilateral axillary nodal metastasis that developed in a patient previously treated for a primary ethmoidal squamous cell carcinoma. To our knowledge, there have only been five case reports in the English literature, accounting for a total of 10 patients, which documented a clinically apparent metastasis to axillary lymph nodes from various head and neck malignancies. Significantly however, the simultaneous ipsilateral and contralateral lymphatic spread of disease from a tumour in the para-nasal sinus, so as to involve bi-axillary nodes, has not been previously reported. We discuss the possible pathogenesis and the prognostic significance of this manifestation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Recurrent nodal metastases in the posterior triangle: implications for treatment of the atypical tumour.

We studied the incidence of recurrent nodal metastases in level V (posterior triangle) in patients who had previously had a staging or therapeutic dissection of the neck, with or without postoperative radiotherapy. Of 160 patients studied (177 neck dissections), 41 (26%) developed recurrent metastases in the neck. Four patients (3%) developed ipsilateral recurrent disease in level V. In these four patients, level III or IV lymph nodes were shown histologically to have extracapsular spread at the time of the original dissection. All four metastases were located at or just beyond the anatomical boundaries of the posterior triangle. None of the metastases at level V were from oral or oropharyngeal primary tumours.

Adult↗
PubMed2004

The skeletal stability of one-piece Le Fort 1 osteotomy to advance the maxilla; Part 1. Stability resulting from non-bone grafted rigid fixation.

During the past decade, we have increasingly preferred to do a one-piece Le Fort 1 osteotomy to advance the maxilla, sometimes in isolation to treat patients with maxillary retrusive skeletal Class III patients or combined with mandibular advancement to treat bimaxillary retrusive skeletal Class II. Clinical impressions of rigid fixation techniques have indicated that there is improved stability when compared with wire fixation. There are few studies in the literature that have addressed relapse following one-piece Le Fort 1 osteotomy to advance the maxilla. Such surgery involves one single spatial movement and thereby eliminates other possible surgical variables, which may impact on the degree of stability achievable postoperatively. We studied 45 patients who had undergone a uniform one-piece maxillary advancement with elimination of controllable variables, apart from 15 patients who had simultaneous mandibular advancement. Rigid fixation was adopted throughout the study. The mean surgical change documented was 7.42 mm. The mean stability calculated at 12 months revealed a relapse of 0.72 mm (10%). This was not significant (P = 0.3). We conclude that the Le Fort 1 advancement osteotomy is a stable and surgically predictable procedure that gives only slight relapse at 12 months.

Adolescent↗
PubMed2004

The skeletal stability of one-piece Le Fort 1 osteotomy to advance the maxilla; Part 2. The influence of uncontrollable clinical variables.

The stability of orthognathic surgery has been the subject of numerous publications over the last 20 years. It is now apparent that studies must pay attention to the homogeneity of the patients investigated and in particular, surgical techniques. In Part 2 of our study of 45 patients who had a uniform one-piece maxillary advancement with rigid fixation to advance the maxilla, we found that uncontrollable variables, including patients age, sex, the degree of advancement, and simultaneous mandibular advancement, had no effect on post-operative skeletal stability.

Adolescent↗
PubMed2004

Does administration of isosorbide mononitrate affect cellular proliferation in oral squamous cell carcinoma? A prospective randomized clinical study.

PURPOSE: There has been much interest in the role that the signaling molecule nitric oxide (NO) plays in cancer. NO has both tumor-promoting and tumor-inhibiting effects that are dependent on its local tissue concentration. In animal studies, the administration of exogenous NO has reduced both tumor growth and dissemination, and in vitro NO administration causes death of oral cancer cell lines. We evaluated the oral administration of the NO donor drug isosorbide mononitrate (ISMO) on cellular proliferation in patients with oral squamous cell carcinoma. MATERIALS AND METHODS: A prospective randomized double-blind study was performed on 31 patients with biopsy-confirmed oral squamous cell carcinoma. Following incisional biopsy, patients were randomized to receive either ISMO (at a dose of 20 mg twice a day) or placebo tablets for 2 weeks before definitive resection. Cellular proliferation was compared between biopsy and resection specimens, using the immunohistochemical marker Ki-67. RESULTS: No statistical difference was found between Ki-67 indices in initial biopsy and resection specimens after ISMO (P =.23) or placebo (P =.5) administration. There were no obvious clinical changes seen in the tumor during the clinical trial as a result of ISMO administration. CONCLUSION: Although high concentrations of NO are cytotoxic, it is unlikely that administration of NO at an increased dose would be useful in the management of oral cancer because this would result in unacceptable systemic side effects. The possible manipulation of NO in oral cancer is discussed.

Adult↗
PubMed2004

Falls in elderly people that result in facial injuries.

Falls in elderly people are increasing. Injuries of the upper limb that result from a fall usually suggest that an outstretched hand was used to curb the fall. Conversely, maxillofacial injuries in elderly people may result from alterations in consciousness as a result of a pre-existing medical condition. We investigated the nature of falls in an elderly population and compared two cohorts of patients-those presenting with maxillofacial injuries, and those with isolated upper limb injuries, and there were 25 patients in each cohort. Comprehensive personal data and medical history were recorded together with details of the fall. We found a significant correlation between the nature of the injury and recollection of the event (P <0.01). Patients who sustain facial injuries are less likely to recall the event. This may be the result of the injury itself, but an underlying medical condition may have been responsible for the fall and should be excluded.

Accidental Falls↗
PubMed2000

Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI.

The RhoGDI proteins serve as key multifunctional regulators of Rho family GTP-binding proteins. The 2.6 A X-ray crystallographic structure of the Cdc42/RhoGDI complex reveals two important sites of interaction between GDI and Cdc42. First, the amino-terminal regulatory arm of the GDI binds to the switch I and II domains of Cdc42 leading to the inhibition of both GDP dissociation and GTP hydrolysis. Second, the geranylgeranyl moiety of Cdc42 inserts into a hydrophobic pocket within the immunoglobulin-like domain of the GDI molecule leading to membrane release. The structural data demonstrate how GDIs serve as negative regulators of small GTP-binding proteins and how the isoprenoid moiety is utilized in this critical regulatory interaction.

Amino Acid Sequence↗
PubMed1998

Fluoride activation of the Rho family GTP-binding protein Cdc42Hs.

Aluminum tetrafluoride (AlF4-) activation of heterotrimeric G-protein alpha-subunits is a well established aspect of the biochemistry of these proteins; however, until recently it has been thought that AlF4- does not mediate effects on the Ras superfamily of low molecular weight GTP-binding proteins. Recent work demonstrating aluminum fluoride-induced complex formation between Ras and its GTPase-activating proteins (RasGAP and NF1) has provided important insights into the mechanism of GAP-stimulated GTP hydrolysis. We have characterized the AlF4--induced complex formation between the GDP-bound form of the Rho subfamily G-protein Cdc42Hs and a limit functional domain of the Cdc42-GAP using a variety of biochemical techniques. Our results indicate that the apparent affinity of GAP for the AlF4--mediated complex is similar to the affinity observed for the activated (GTP-bound) form of Cdc42 and that beryllium (Be) can replace aluminum in mediating fluoride-induced complex formation. Additionally, the AlF4--induced interaction is weakened significantly by the catalytically compromised GAP(R305A) mutant, indicating that this arginine is critical in transition state stabilization. Unlike Ras, we find that AlF4- and BeF3- mediate complex formation between Cdc42Hs.GDP and downstream target/effector molecules, indicating that there are important differences in the mechanism of effector binding between the Ras and Rho subfamily G-proteins.

Aluminum Compounds↗
PubMed1998

Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP.

The Rho-related small GTP-binding protein Cdc42 has a low intrinsic GTPase activity that is significantly enhanced by its specific GTPase-activating protein, Cdc42GAP. In this report, we present the tertiary structure for the aluminum fluoride-promoted complex between Cdc42 and a catalytically active domain of Cdc42GAP as well as the complex between Cdc42 and the catalytically compromised Cdc42GAP(R305A) mutant. These structures, which mimic the transition state for the GTP hydrolytic reaction, show the presence of an AIF3 molecule, as was seen for the corresponding Ras-p120RasGAP complex, but in contrast to what has been reported for the Rho-Cdc42GAP complex or for heterotrimeric G protein alpha subunits, where AIF4- was observed. The Cdc42GAP stabilizes both the switch I and switch II domains of Cdc42 and contributes a highly conserved arginine (Arg 305) to the active site. Comparison of the structures for the wild type and mutant Cdc42GAP complexes provides important insights into the GAP-catalyzed GTP hydrolytic reaction.

Aluminum Compounds↗
PubMed1996

Mutagenicity of acridines in a reversion assay based on tetracycline resistance in plasmid pBR322 in Escherichia coli.

The mutagenicity of a series of acridine compounds was studied in an assay based on the reversion of mutations in the tetracycline-resistance gene (tet) of plasmid pBR322 in Escherichia coli. Mutations that restore the tetracycline-resistant phenotype were detected in tetracycline-sensitive strains carrying mutant plasmids. Mutations that revert by +2, +1, -1 and -2 frameshift mutations and by base-pair substitutions were used to analyze the mutagenicity of two simple acridines, two acridine mustards, and a nitroacridine. The simple acridines (9-aminoacridine and quinacrine) effectively induced -1 frameshifts and weakly induced +1 frameshifts. The acridine mustards (quinacrine mustard and ICR-191) were more potent inducers of -1 and +1 frameshifts than the simple acridines. Reactive acridines, including both the mustards and the nitroacridine Entozon, were effective inducers of -2 frameshifts but the simple acridines were not. The two classes of reactive acridines differed from one another, in that the mustards were better inducers of +1 frameshifts than Entozon, whereas Entozon was a particularly potent inducer of -2 frameshifts. None of the compounds induced +2 frameshifts, and the induction of base-pair substitutions was negligible. These results confirm and extend studies showing that adduct-forming acridines are stronger frameshift mutagens than simple intercalating acridines and that the acridines differ from one another not only in overall mutagenic potency but also in the prevalence of different classes of frameshift mutations.

Acridines↗
PubMed1996

The stability of facial osteotomies. Part 6. Chin setback.

Isolated horizontal osteotomy of the anterior mandible (genioplasty) to move the chin posteriorly can be used to improve facial profile. There has been an increasing tendency in practice to carry out this procedure in combination with maxillary and/or mandibular surgery. This is most appropriately undertaken when pre-operative prediction techniques indicate that chin prominence will remain excessive following maxillary and/or mandibular advancement surgery. This paper reviews surgical techniques applicable to posterior movement of the chin ("the setback genioplasty') and illustrates the clinical results achieved with its use.

Adolescent↗
PubMed1996

The stability of facial osteotomies. Part 5. Maxillary advancement with miniplate and screw fixation.

Surgical repositioning of the dento-skeletal components of the middle-third of the face, combined with appropriate orthodontic treatment, can be used to improve function and aesthetics. However, the attainment of three-dimensional stability following corrective jaw surgery continues to be a major problem in the postsurgical period. This paper examines the short-term (six weeks postoperative) and long-term (12 months postoperative) horizontal skeletal stability of Le Fort I maxillary advancement in 15 patients. The mean horizontal advancement of the maxilla was 8.76 +/- 0.99 mm. Six weeks later, a mean relapse of 0.22 +/- 0.19 mm was identified. The mean relapse at long-term follow-up was 0.61 +/- 0.26 mm (6.96%). These results indicate that rigid miniplate and screw fixation of Le Fort I osteotomy undertaken to correct horizontal mid-dentofacial deficiency is both statistically and surgically predictable and stable when reviewed up to twelve months after surgery.

Adolescent↗
PubMed1995

The stability of facial osteotomies. 2. Mandibular advancement with bicortical screw fixation.

Surgical repositioning of the dento-skeletal components of the lower third of face, combined with appropriate orthodontic treatment, can be used to improve function and aesthetics. However, the attainment of three-dimensional stability following corrective jaw surgery continues to be a major problem in the post-surgical period. This paper examines the short-term (6 week post-operative) and long-term (12 months postoperative) horizontal skeletal stability of bilateral sagittal split mandibular advancement in 15 patients. The mean horizontal advancement of the mandible was 6.1 mm. Six weeks later, a mean continued forward movement of 0.16 mm was identified. The mean relapse at long-term follow-up was 0.46 mm (7.5%). Results indicate that rigid bicortical screw fixation of bilateral sagittal split osteotomies undertaken to correct horizontal lower dentofacial deficiency is both statistically and surgically predictable and stable when reviewed up to twelve months after surgery.

Adolescent↗