The curious case of the orange coloured tonsils.

Tangier disease is an extremely rare and severe form of high density lipoprotein deficiency. Even though there is no specific therapy for patients with Tangier disease, it is important to recognize the clinical presentation as patients are at an increased risk of developing atherosclerosis and subsequent CVD. The case discussed in this report, illustrates the importance of recognizing that orange discoloured tonsils are an indication that the patient could be suffering from Tangier's disease.

Aldose reductase structures: implications for mechanism and inhibition.

During chronic hyperglycaemia, elevated vascular glucose level causes increased flux through the polyol pathway, which induces functional and morphological changes associated with secondary diabetic complications. Inhibitors of aldose reductase (ARIs) have been widely investigated as potential therapeutic agents, but to date only epalrestat is successfully marketed for treatment of diabetic neuropathy, in Japan. Promising compounds during in vitro studies or in trials with animal models have failed to proceed beyond clinical trials and to everyday use, due to a lack of efficacy or adverse side effects attributed to lack of inhibitor specificity and likely inhibition of the related aldehyde reductase (ALR1). Knowledge of the catalytic mechanism and structures of the current inhibitors complexed with ALR2 are means by which more specific and tightly bound inhibitors can be discovered. This review will provide an overview of the proposed catalytic mechanism and the current state of structure-based drug design.

Sorbitol dehydrogenase: structure, function and ligand design.

Sorbitol dehydrogenase (SDH), a member of the medium-chain dehydrogenase/reductase protein family and the second enzyme of the polyol pathway of glucose metabolism, converts sorbitol to fructose strictly using NAD(+) as coenzyme. SDH is expressed almost ubiquitously in all mammalian tissues. The enzyme has attracted considerable interest due to its implication in the development of diabetic complications and thus its tertiary structure may facilitate the development of drugs for the treatment of diabetes sufferers. Modelling studies suggest that SDH is structurally homologous to mammalian alcohol dehydrogenase with respect to conserved zinc binding motif and a hydrophobic substrate-binding pocket. Recently, the three-dimensional (3-D) structure of a mammalian SDH was solved, and it was found that while the overall 3-D structures of SDH and alcohol dehydrogenase are similar, the zinc coordination in the active sites of the two enzymes is different. The available structural and biochemical information of SDH are currently being utilized in a structure-based approach to develop drugs for the treatment or prevention of the complications of diabetes. This review provides an overview of the recent advances in the structure, function and drug development fields of sorbitol dehydrogenase.

The ultra-low resistance Groningen voice prosthesis: clinical experiences.

The performance of the ULR Groningen prosthesis was assessed in 21 laryngectomees. The intratracheal phonatory pressures (PITP), voice parameters (speech rate, maximal phonation time, maximal vocal intensity, dynamic vocal intensity range), device lifetime and patient's subjective acceptances were recorded and compared to identical parameters for other prostheses reported in the literature and to data obtained from an age-matched group of normal laryngeal speakers. The low airflow resistance of the ULR Groningen voice prosthesis objectively (PITP = 2.7 kPa) and subjectively leads to a low effort to phonate. Compared to "normals" maximal phonation time shows no significant difference, but speech rate, maximal vocal intensity and dynamic vocal intensity range show a significant worse outcome. The mean device lifetime of the ULR Groningen prosthesis is more than 13.6 weeks, which is comparable to other indwelling voice prostheses. In conclusion, the ULR Groningen voice prothesis enables easier tracheoesophageal phonation than the low-resistance Groningen type.

Laparoscopic extracorporeal oophorectomy and ovarian cystectomy in second trimester pregnant obese patients.

OBJECTIVES: To determine whether a modified technique for laparoscopic extracorporal oophorectomy is less complicated and safer than traditional laparoscopic oophorectomy. METHODS: Four obese patients in their second trimester underwent open laparoscopy for treatment of large ovarian cysts. A Cook Ob/Gyn special cyst aspirator with a 14-gauge aspirating needle was inserted into the abdomen to drain the ovary through a separate 10-mm port; the site of insertion depends on the location of the ovary. After the cyst was decompressed, the 10-mm incision was enlarged to 3 cm, and either extracorporal oophorectomy or cystectomy was performed. RESULTS: No complications occurred. Average blood loss was less than 15 cc; average carbon dioxide insufflation time was less than 20 minutes. Average operating time was 40 minutes, which was significantly less than traditional laparoscopic oophorectomy. The patients were discharged in less than 23 hours. Patient A had a 500-cc dermoid cyst, and subsequently had a normal vaginal delivery at term. Patient B had a 1600-cc cyst removed. She had a cesarian delivery due to cephalopelvic disproportion. Pathological analysis of the specimen identified the mass as a dermoid cyst and serous cystadenoma. Patient C had a 3200-cc ovarian cyst. Currently, she is in her 24th week of gestation. Patient D had a 700-cc simple ovarian cyst removed at her 16th week of gestation. CONCLUSIONS: Laparoscopic extracorporal oophorectomy requires significantly less CO2 insufflation time and a shorter operation time, hence, decreasing the adverse effects on the fetus. The enlarged second trimester uterus made traditional laparoscopy more complicated. Performing the procedure extracorporally decreased the possibility of operative complications.

Aldose and aldehyde reductases: correlation of molecular modeling and mass spectrometric studies on the binding of inhibitors to the active site.

Aldose and aldehyde reductases are monomeric NADPH-dependent oxidoreductases that catalyze the reduction of a wide variety of aldehydes and ketones to their corresponding alcohols. The overall three-dimensional structures of the enzymes are composed of similar alpha/beta TIM-barrels, and the active site residues Tyr 50, His 113, and Trp 114 interacting with the hydrophilic heads of inhibitors are conserved. We have used molecular modeling and mass spectrometry to characterize the interactions between the enzymes and three aldose reductase inhibitors: tolrestat, sorbinil, and zopolrestat. Unlike the IC(50) values (concentration of inhibitor giving 50% of inhibition in solution), the Vc(50) values measured by mass spectrometry (accelerating voltage of ions needed to dissociate 50% of a noncovalent complex in the gas phase) for the two enzymes are similar, and they correlate with the electrostatic and hydrogen-bonding energies calculated between the conserved Tyr 50, His 113, and Trp 114 and the inhibitors. The results of our comparison agree with detailed structural information obtained by X-ray crystallography, suggesting that nonconserved residues from the C-terminal loop account for differences in IC(50) values for the two enzymes. Additionally, they confirm our previous assumption that the Vc(50) values reflect the enzyme-inhibitor electrostatic and hydrogen-bonding interactions and exclude the hydrophobic interactions.

The ultra-low resistance Groningen voice prosthesis: aerodynamic properties.

Post-laryngectomy voice rehabilitation using the low resistance (LR) Groningen voice prosthesis has over the past years provided good voice and speech results. The valve part of the prosthesis is largely responsible for the airflow resistance of the prosthesis. This study was performed to evaluate if by modifying the valve part of the LR Groningen prosthesis a lower airflow resistance in vitro could be achieved. Several prototypes with modified valves were tested. Based on the aerodynamic measurements the prosthesis with a single slit of 200 degrees in the 'hat' of the esophageal flange was selected for further evaluation and named the ultra-low resistance (ULR) Groningen voice prosthesis. Aerodynamic measurements were performed and showed the airflow resistance of the ULR Groningen voice prosthesis to be significantly lower than the resistance of the LR Groningen and the Provox voice prostheses.

[Tuberculosis of the larynx]. / Tuberculose in de larynx.

Laryngeal tuberculosis was diagnosed in two men, a 73-year-old man Dutch by birth and a 40-year-old one Turkish by birth. In the former patient it was probably primary tuberculosis, in the latter secondary (he had lung tuberculosis as well). The clinical picture was highly suggestive of laryngeal carcinoma in both patients. They both recovered with chemotherapy. Laryngeal tuberculosis may mimic laryngeal carcinoma. The diagnosis is based on Ziehl-Neelsen staining, culture and polymerase chain reaction (PCR) on Mycobacterium tuberculosis. Because laryngeal tuberculosis is highly infectious, the patient has to be nursed in isolation and people in his or her environment have to be screened. The response of laryngeal tuberculosis to chemotherapy is good.

In vitro and in vivo comparison of the low-resistance Groningen and the Provox tracheosophageal voice prostheses.

This study has been performed to evaluate and compare two frequently used indwelling tracheoesophageal voice prostheses, the low-resistance (LR) Groningen and the Provox voice prosthesis. The airflow resistance in vitro of the Provox prosthesis has been measured and compared to our reported results of the LR Groningen prosthesis. The in vivo study involved fifteen non-myotomized laryngectomees who randomly received one of the two prostheses. Measurements were performed of the intratracheal phonatory pressure and of voice parameters. The intelligibility of speech in noise was evaluated in eight patients. Patients preferences regarding the two prostheses were assessed. Aerodynamic measurements show the Provox voice prosthesis to have a lower airflow resistance. The median intratracheal phonatory pressure for phonation of 75 dB was significantly lower (2.1 kPa) in patients using the Provox voice prosthesis. Speech rate, maximal phonation time and maximal vocal intensity showed no significant difference. The intelligibility of speech in noise produced with the Provox was significantly better than the speech produced with the LR Groningen prosthesis. Subjectively, most patients preferred the Provox prosthesis because speech required less effort. Patients with a hypotonic pharyngoesophageal segment tended to prefer the LR Groningen prosthesis.

A new method for in vivo evaluation of biofilms on surface-modified silicone rubber voice prostheses.

A new method is presented that permits a rapid and accurate in vivo evaluation of biofilm formation on surface-modified silicone rubber voice prostheses. The method is based on partial modification of a Groningen button voice prosthesis by exposing half of the prosthesis to an argon plasma. This results in one side of the prosthesis becoming hydrophilic while leaving the unmodified side hydrophobic as a control. Modified prostheses were placed in patients for an evaluation period of approximately 4 weeks. Despite making the silicone rubber surface hydrophilic, biofilm formation was stimulated when compared to unmodified, hydrophobic silicone rubber. Findings show that biofilm formation on voice prostheses is influenced by hydrophobicity of a silicone rubber surface. The method of partial surface modification used was seen to be suitable for demonstrating such influences regardless of nutrition and other variations in the patient's lifestyle. Microbiological analysis of the biofilms on both sides of the prosthesis valve did not show any changes in microbial composition, with Candida albicans, streptococci and staphylococci being the most commonly isolated strains.

Antibodies prevalence against HPV-6b and -16 recombinant fusion proteins in Korean patients with cervical neoplasia.

OBJECTIVES: This study was to investigate the adjunctive diagnostic utility of HPV fusion proteins from the sera in the patients with cervical neoplasia. Immunologic researches on host factors in HPV infection could contribute to better understanding of patho-physiologic mechanisms of cervical carcinogenesis, and provide valuable information for HPV vaccine development. METHODS: Prevalence of antibodies against human papillomavirus (HPV) in sera of the patients with carcinoma (n = 81), precancers (n = 25) of uterine cervix and normal controls (n = 40) in Korean women were investigated by Western blot immunoassay using partially purified TrpE fusion recombinant proteins for HPV-6b and HPV-16. RESULTS: In 81 patients with cervical cancer, 15 (19%) and 54 (67%) patients were positive for antibodies to at least one of the tested recombinant proteins related to HPV-6b or HPV-16, respectively. And in 25 patients with HPV-related squamous intraepithelial lesion (SIL) of cervix, 10 were positive for at least one of the tested antibodies for HPV-6b gene products (40%) and 11 were positive for HPV-16 related antibodies (44%). The prevalence rates of antibodies for HPV-6b in the sera of SIL patients were significantly higher than those from the sera of cervical cancer patients (p < 0.05). There was an inverse correlation between increasing the positivity against HPV-16 E6 protein and progression of cervical lesions, but there was no significant correlation between the positivities of the other antibodies to HPV-16 and the severity of disease. CONCLUSION: These results suggest that the recombinant proteins related to HPV-6b and HPV-16 could be useful in evaluation of the patients with HPV-related cervical lesions and these might play an adjunctive role in diagnosis and management of cervical neoplasia.