Adrenoleukodystrophy in Norway: High Rate of De Novo Mutations and Age-Dependent Penetrance

To investigate X-linked adrenoleukodystrophy in an unselected population, we performed a population based, cross-sectional prevalence study, supplemented by a retrospective study of deceased subjects. Sixty-three subjects (34 males, 29 females) belonging to 22 kindreds were included. Thirty-nine subjects (13 males, 26 females) were alive, and 24 (21 males, 3 females) were deceased on the prevalence day. The point prevalence of X-linked adrenoleukodystrophy in Norway on July 1, 2011, was 0.8 per 100,000 inhabitants. The incidence at birth in the period 1956-1995 was 1.6 per 100,000 inhabitants. An age-dependent penetrance was observed among males and females, with more severe phenotypes appearing with rising age. Only 5% of deceased males had not developed cerebral leukodystrophy. No female older than 50 years was neurologically intact. Sixteen mutations in the ABCD1 gene were identified. De novo mutations were found in 19% of probands. The frequency of X-linked adrenoleukodystrophy was lower in Norway than reported in the literature. A more severe natural course than previously reported was observed, indicating a need for better follow-up of both male and female patients. Given the high rate of de novo mutations, identification programs such as newborn screening may be required to offer timely treatment to all patients.     

Doxycycline hydrochloride-metronidazole solid lipid microparticles gels for treatment of periodontitis: development,in-vitro and in-vivo clinical evaluation

Objective: To formulate solid lipid microparticles (SLMs) encapsulating doxycycline hydrochloride (DH) and metronidazole (MT) for the treatment of periodontal diseases.

Methods: SLMs were prepared applying hot homogenization method, using different types of lipids and stabilized with various types and concentrations of surfactants. The optimized formula was subjected to freeze-drying followed by incorporation into poloxamer gel. Microbiological and clinical evaluation of the selected SLMs on patients suffering from periodontal diseases was performed.

Results: SLMs could entrap high percentage of both drugs (81.14% and 68.75 % for doxycycline hydrochloride and metronidazole respectively). Transmission electron microscopy images of SLMs showed nearly spherical particles. Freeze-dried SLMs showed satisfactory stability for three months. Combined drugs were molecularly dispersed in SLMs. Incorporation of the freeze-dried SLMs powder in poloxamer gel could control the drugs release for 72 h. In-vivo study revealed effective and safe use of SLMs gel for periodontitis treatment. Significant improvement in both microbiological and clinical parameters was observed as compared to scaling and root planing alone.

Conclusion: The formulated SLMs gel offers an applicable dosage form that can be injected directly into the periodontal pocket as adjunctive to scaling and root planing.     

Long-Term Surveillance of Treated Hyperparathyroidism for Multiple Endocrine Neoplasia Type 1: Recurrence or Hypoparathyroidism?

Background

Primary hyperparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1) is surgically treated with either a subtotal parathyroidectomy removing 3 or 3,5 glands (SPX), less than 3 glands (LSPX), or a total parathyroidectomy with autotransplantation (TPX). Previous studies with shorter follow-up have shown that LSPX and SPX are associated with recurrent HPT, and TPX with hypocalcemia and substitution therapy. We examined the situation after long-term follow-up (median 20,6 years).

Methods

Sixty-nine patients with MEN1 HPT underwent 110 operations, the first operation being 31 LSPX, 30 SPX, and 8 TPX. Thirty patients underwent reoperative surgery in median 120 months later, as completion to TPX (n = 12), completion of LSPX to SPX (n = 9), extirpation of single glands (n = 3) still resulting in LSPX, and resection of forearm grafts (n = 3). Nine patients underwent a second, and 2 a third reoperation. In 24 patients genetic testing confirmed MEN1, and in the remaining heredity and phenotype led to the diagnosis.

Results

TPX had higher risk for hypoparathyroidism necessitating substitution therapy, at latest follow-up 50 %, compared to SPX (16 % after 3–6 months; none at latest follow-up). Recurrent HPT was common after LSPX, leading to 24 reoperations in 17 patients. No need for substitution therapy after SPX indicated forthcoming recurrent disease. Not having hypocalcemia in the postoperative period and less radical surgery than TPX were significantly associated to risk for recurrence. Further, mutation in exon 3 in the MEN1 gene may eventually be linked to risk of recurrence.

Conclusion

LSPX is highly associated with recurrence and TPX with continuous hypoparathyroidism, also after long-term follow-up. SPX should be the chosen method in the majority of patients with MEN1 HPT.

     

Recent advances in optical diagnosis of oral cancers: Review and future perspectives

Optical diagnosis techniques offer several advantages over traditional approaches, including objectivity, speed, and cost, and these label‐free, noninvasive methods have the potential to change the future workflow of cancer management. The oral cavity is particularly accessible and, thus, such methods may serve as alternate/adjunct tools to traditional methods. Recently, in vivo human clinical studies have been initiated with a view to clinical translation of such technologies. A comprehensive review of optical methods in oral cancer diagnosis is presented. After an introduction to the epidemiology and etiological factors associated with oral cancers currently used, diagnostic methods and their limitations are presented. A thorough review of fluorescence, infrared absorption, and Raman spectroscopic methods in oral cancer diagnosis is presented. The applicability of minimally invasive methods based on serum/saliva is also discussed. The review concludes with a discussion on future demands and scope of developments from a clinical point of view. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E2403–E2411, 2016     

Prevalence of HIV infection and uptake of HIV/AIDS services among fisherfolk in landing Islands of Lake Victoria,north western Tanzania

Background

New HIV infections in Tanzania have been decreasing, however some populations remain at higher risk. Despite of that, evidence on the magnitude of HIV infection and the associated factors and HIV/AIDS services uptake among fisherfolk in Tanzania are inadequately explored. This study therefore aimed at determining prevalence of HIV infection and utilization of HIV/AIDS services among fishfolk in selected Islands of Lake Victoria for evidence-based interventions.

Methods

Cross-sectional study determining status of HIV infection among fisherfolk (n?=?456) and retrospective review of voluntary counselling and testing (VCT) registry (n?=?1744) were done in Buchosa and Muleba districts. Structured questionnaire and HIV rapid test kits with the standard testing protocol were used as research tools.

Results

A total of 269 (58.9%) male and 187 (41.1%) female fisherfolk were recruited during the community survey. Prevalence of HIV infection was 14% in all surveyed landing sites with a site variation from as low as 7.2% to as high as 23.8%. Participants employed in fishing related employment had higher odds of being HIV infected (5.4 times) than those who practiced fishing and partly farming [OR?=?5.40; 95%CI 1.88–15.61; p?<?0.001]. Participants employed in fishing related employment had higher odds of being HIV infected (5.4 times) than those practiced fishing and farming [OR?=?5.40; 95%CI 1.88–15.61; P?<?0.001]. Lack of formal education [aOR?=?3.37; 95%CI 1.64–6.92; p?<?0.001], being older [aOR?=?1.06; 95%CI 1.03–1.09] and using alcohol [aOR?=?2.26; 95%CI 1.23–4.15] predicted the likelihood of contracting HIV infection. Approximately three quarters (76%) of respondents had ever tested for HIV infection within past 1 year. Moreover, about half of the study participants had used condom inconsistently and 5 out of 14 (37.5%) of participants who knew their status had never started treatment. Despite the low uptake of most HIV preventive services, majority (88%) of male fisherfolk were circumcised.

Conclusion

The magnitude of HIV infection among fisherfolk was up to 3 times higher than that of the general populations in Muleba and Buchosa districts. Higher age, using alcohol and lack of formal education predicted increased likelihood of HIV infection. The uptake of key HIV/AIDS curative and preventive services was generally low.

     

Abnormal lung function in healthy preterm infants.

The aim of this study was to assess the consequences of preterm birth for the functional development of the lungs. We studied 32 healthy preterm infants (gestational age 25 to 33 wk at birth) and 53 healthy full-term infants (37 to 42 wk) at the same mean postmenstrual age of 40 wk with a multibreath nitrogen washout technique to assess functional residual capacity (FRC), gas mixing efficiency, and dead space and with the single-breath occlusion technique to calculate compliance and resistance of the respiratory system. Twenty of the preterm infants were also assessed with the same methods at 34.2 (32 to 37) wk. At the same postmenstrual age the preterm infants had lower FRC/kg body weight, lower specific compliance, impaired gas mixing efficiency, and higher total and dead space ventilation/kg than the full-term infants. Specific compliance and specific conductance decreased but gas mixing efficiency increased from 34 to 40 wk. We conclude that premature exposure to extrauterine conditions changes lung function. Preterm infants showed signs of dysfunction of the terminal respiratory units and higher elastic recoil than infants who spent the corresponding time for development in utero. It is suggested that preterm birth per se affects alveolarization and formation of elastic tissue in the lungs.     

Proximal subcutaneous interstitial fluid pressure during cross-clamping of the descending thoracic aorta: A study of patients operated on for thoracic-or thoracoabdominal aortic aneurysms

Seven patients were operated on for thoracic (n=2) or thoracoabdominal (n=5) aortic aneurysms during cross-clamping of the aorta. Interstitial tissue fluid pressure was measured at the neck during cross-clamping of the descending thoracic aorta by the wick-in-needle technique, whereas control measurements were obtained prior to cross-clamping. The subcutaneous interstitial fluid pressure was significantly higher on the neck during cross-clamping of the thoracic aorta compared with control measurements (median 3.7 mmHg vs –0.6 mmHg, p<0.05). Increased subcutaneous interstitial tissue pressure of the upper part of the body is probably caused by increased capillary filtration rate induced by inhibited autoregulatory functions during aortic cross-clamping. The pressure measurements objectively confirm the problem of edema formation of the head and neck during these operations. The edema may occasionally affect the upper airways and represent a problem for intubation of the patient in the postoperative phase.