Conservative Surgery in T3–T4 Pharyngolaryngeal Squamous Cell Carcinoma: An Alternative to Radiation Therapy and to Total Laryngectomy for Good Responders to Induction Chemotherapy

Objective To evaluate the possibility of preservation of the larynx after neoadjuvant chemotherapy by performing a conservative surgery instead of total laryngectomy initially planned, in patients with previously untreated laryngeal and piriform sinus squamous cell carcinoma (SCC). Study Design Retrospective study. Methods A total of 115 patients treated at Tenon Hospital with induction chemotherapy from 1985 to 1995, all with initial indication of radical surgery, were available for the study. The clinical tumor response was evaluated after three cycles of chemotherapy. According to this response, to preserve laryngeal functions, some patients had a modification of the treatment initially planned: radiation therapy essentially for complete responders, and conservative surgery for some partial responders. Results Of 69 patients with laryngeal cancer, 14 were treated by partial laryngectomy and 19 by radiation therapy; of 46 patients with piriform sinus cancer, 8 were treated by partial surgery and 12 by radiation therapy; the other patients were treated as was initially planned (total laryngectomy with partial pharyngectomy). Overall survival rates, estimated by the Kaplan‐Meier method, were not statistically different between the three treatment groups. The laryngeal functions were preserved in 54% of the patients who were alive at 3 years. Conclusion This report is a retrospective study, but these results suggest the possibility of using conservative surgery, instead of initially planned total laryngectomy, for good responders to induction chemotherapy with a small residual tumor.     

Re‐evaluation of normative electronystagmography data in healthy ageing

Previous work by our group questions the validity of existing electronystagmography ( eng ) reference ranges in the elderly. We aim to establish valid reference ranges for eng in people over 65 on the Nicolet Nystar Plus system. Ninety‐six healthy asymptomatic subjects over 65 underwent eng , including spontaneous and positional nystagmus, saccades, smooth pursuit, optokinetic nystagmus and bithermal calorics; 95% reference ranges with confidence intervals were calculated. The newly determined reference ranges were far wider than those provided by the eng equipment manufacturer for eight out of 11 parameters (all P < 0.001). Vestibular function is known to deteriorate and become more variable with age. The failure to reflect this change in currently used reference ranges may have contributed to the high rates of vestibular disease reported in some series of dizzy elderly patients. Clinical interpretation of eng depends on valid reference ranges.     

Work-place screening of mine employees using the alcohol use disorders identification test (AUDIT) and alcohol breathalyzation

Although public health campaigns focusing on alcohol in the work-place are receiving increasing attention, there is little empirical evidence regarding the use of screening. In this work-place study, 152 mining personnel (67% of the work-force) completed a self report screen using the Alcohol Use Disorders Identification Test (AUDIT). One hundred and thirty-three of these (58.5% of the work-force) also consented to be breathalysed and one (0.75%) recorded a BAC just over threshold for detection. Forty-eight males (37.7% of the male work-force) recorded AUDIT scores of eight or more consistent with hazardous alcohol use and one female registered a cumulative score above the female cut-off level for hazardous alcohol use. Eighty males (67% of the work-force), recorded binge drinking at least monthly and 81 males recorded a cumulative AUDIT score of less than eight; however, on item analysis, 64 (83%) of these recorded binge drinking at least sometimes. There is substantial hazardous alcohol use in this sample work group and younger males had higher alcohol consumption, more adverse consequences and higher total AUDIT scores identifying them as particularly at risk. The Cronbach & AUDIT was 0.72, confirming adequate internal consistency.     

Gene directed enzyme prodrug therapy for cancer

One strategy for gene therapy in malignant disease is gene directed enzyme prodrug therapy (GDEPT). An exogenous enzyme gene is delivered to tumour cells. The enzyme, when expressed, can convert a non-toxic prodrug into a cytotoxic species that is capable of killing the cell in which it has been produced. The most frequently used systems are HSV thymidine kinase with ganciclovir and E. coli cytosine deaminase with 5-fluorocytosine. The bystander effect is of key importance to GDEPT: This describes the local spread of active species from cells that express the enzyme to kill adjacent, untransduced cells. The ultimate success of GDEPT will depend on the ability to achieve efficient gene delivery to and expression in target cells, whilst minimising expression in other tissues. A variety of techniques exist to achieve this goal, including loco-regional administration, manipulation of tumour blood supply and use of tumour-specific promoters to drive enzyme gene expression.     

Changes of nitric oxide synthase activity and free methylarginines contents in regenerating rat liver after partial hepatectomy

In the present study, liver regeneration rate (%) was increased up to 70% 3 days after partial hepatectomy (PH). Nitric oxide synthase (NOS) activity in liver tissue as well as serum nitrite/nitrate content had no timed response, revealing no significant difference between shamoperated and partially hepatectomized rat liver. Contents of free methylarginines in liver tissue were increased biphasically in a time-dependent manner after PH. However, those in serum did not exhibit the same patterns as in liver. Taken together, the results suggest that N^G-monomethyl-L-arginine (MMA) and N^G, N^G-dimethylarginine (DMA) play a role in inhibiting nitric oxide (NO) synthesis in regenerating rat liver because the increase of their contents was synchronized with NOS expression.     

Best practices in managing organized delivery systems

The U.S. Department of Veterans Affairs (VA), a large public-sector healthcare delivery system, is following the lead of the private sector in seeking a more integrated approach to providing patient care. The belief is that new entities known as organized delivery systems (ODSs) will produce better, more cost-effective care. Toward this end, VA has reorganized its facilities into 22 networks. The purpose of this paper is to provide VA policymakers and managers with information about building and managing an integrated delivery system for the nation's veterans based on findings from the Health Systems Integration Study (HSIS).     

Metabolism and excretion study of DW116, a new fluoroquinolone, in rats

Metabolite identification and urinary and biliary excretion of the new fluoroquinolone antibacterial agent DW116 [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, hydrochloride] after oral administration have been studied in Sprague-Dawley rats. The excretion kinetics were monoexponential. Most of the drug was eliminated via the hepatic and renal routes. Mean renal clearance of DW116 was 73.4 ml/hr/kg and mean biliary clearance was 83.8 ml/hr/kg. The major metabolite excreted in the bile was identified as the glucuronide ester of the parent drug using base-hydrolysis of the conjugate metabolite followed by co-HPLC with standard compound,¹⁹F-NMR and LC-MS methods. The glucuronide conjugate was also found in urine. The mean urinary recoveries of free and total (free plus glucuronide ester) DW116 were 28.6±2.7% and 36.4±1.8% of the administered dose and the corresponding biliary recoveries were 14.4±5.5% and 37.0±7.6%, respectively.     

Induction of apoptosis in HepG2 human hepatocellular carcinoma cells by a novel derivative of ursodeoxycholic acid (UDCA)

The effects of ursodeoxycholic acid (UDCA) and its novel derivative, named as HS-1030, on the proliferation of HepG2, human hepatocellular carcinoma cells were investigated. Whereas UDCA had no significant effect in a concentration range we have tested, HS-1030 inhibited the proliferation of HepG2 cells in a concentration dependent manner. Surprisingly, HS-1030 had no effect on the proliferation of Human Chang liver cell which is a normal liver cell line. We also found that proliferation-inhibitory effect of HS-1030 was due to the induction of apoptosis of HepG2 cells, which was confirmed by observing the internucleosomal DNA fragmentation and morphological changes (i.e. cell shrinkage, nuclear condensation and the formation of apoptotic bodies). These results suggest that HS-1030 may be a good candidate as a drug for the treatment of liver cancer.     

Inhibitory effects of plant extracts on adjuvant-induced arthritis

Twenty seven plant extracts were selected on the basis of ancient literature search for rheumatoid arthritis or similar syndrome. Methanol extract of each plant was prepared and administered orally to rats everyday at a dose of 200 mg/kg/day. Experimental arthritis was induced by subplantar injection of heat-killedMycobacterium butyricum to right hind paw of rats. This treatment provoked swelling of the treated paw in two phases, acute primary swelling and secondary arthritic swelling. An inhibition of secondary swelling was considered to be antiarthritic activity. Several plant methanol extracts such asAkebia quinata (caulis),Ephedra sinica (herba) andSophorae subprostrata (radix) were found to show significant inhibitory activity against secondary swelling at the dose tested. Our results strongly suggested an antiarthritic potential of these plant extracts.