Parathyroid Neoplasms: The Army Hospital (Research & Referral) Experience

Background

Neoplasms of the parathyroid are common but parathyroid carcinoma is exceptionally rare. In contrast to most other malignant endocrine tumours that are usually less hormonally active, malignant parathyroid tumours are hyper functional. Malignant parathyroid tumours pose a diagnostic dilemma for the pathologist.

Objective

To study the clinicopathological profile of a case series of parathyroid neoplasms and determine features which facilitate a malignant diagnosis.

Methods

A retrospective analysis of seven cases of surgically treated parathyroid tumours over a three-year period at a single centre was done. Clinical, haematological, biochemical, and radiological data was accrued from medical records. The histopathology slides were reviewed along with the clinicopathological profile in an attempt to delineate markers of malignancy.

Results

Patients ranged from 30 to 58 years of age. Males and females were approximately equal. Weakness and bone pain were the commonest presenting symptoms. Over 50% had significant hypercalcaemia and all had elevated serum parathormone. Clinically apparent mass was seen in only one. All tumours were successfully localised using CT scan and MRI. Thick fibrous capsule and broad septal fibrosis was seen in both the carcinomas; these were thin in the adenomas. Mitotic counts of 1-3 per high power field (HPF), capsular invasion and nodal metastasis were noted in the malignant tumours.

Conclusion

Elevated serum calcium and parathormone values point to a parathyroid neoplasm. Current imaging modalities are successful in localising the tumour preoperatively. Markedly elevated serum calcium, broad fibrous bands, mitotic counts and capsular invasion are indicators of malignancy.Key Words: Parathyroid, Adenoma, Carcinoma     

Atrophy of the residual alveolar ridge following tooth loss in an historical population

Oral Diseases (2010) 17 , 33–44 Objectives: To study the natural aetiopathology of jaw atrophy after tooth loss, unaltered by prosthetic procedures, an historical population without modern dental treatment was examined. Methods: Based on the hypothesis that there are predictable changes in shape during jaw‐atrophy, frequency and degree of atrophy as well as clinical aspects of bone quality and resorption were determined in the skeletal remains of 263 individuals. The potential association between age and frequency/severity of atrophy was analysed. Results: Atrophy in at least one jaw segment was present in 45.2% of the analysed jaw specimens. The residual ridge underwent a series of changes in shape and height following the pattern of resorption described for modern populations. The severity of these alterations was associated with the age of the individual and the region within the jaw. Atrophy was frequently related to structural degradation of the covering cortical layer. Conclusions: These findings prove that atrophy of the jaw evidently does occur, displaying similar patterns of resorption in a population without modern prosthetics, where the negative effect of ill‐fitting dentures is excluded. The basic information about alterations of shape and the cortical layer covering the residual crest might help to provide a deeper insight into aetiopathological mechanisms of this common oral disease.     

Interaction between anandamide and sphingosine-1-phosphate in mediating vasorelaxation in rat coronary artery

Background and purpose:

This study establishes a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the time course and in vivo mechanisms of action of the antinociceptive effects of lumiracoxib, evaluated by the thermal hyperalgesia test in rats.

Experimental approach:

Female Wistar fasted rats were injected s.c. with saline or carrageenan in the right hind paw, followed by either 0, 1, 3, 10 or 30 mg·kg⁻¹ of oral lumiracoxib at the time of carrageenan injection (experiment I), or 0, 10 or 30 mg·kg⁻¹ oral lumiracoxib at 4 h after carrageenan injection (experiment II). Antihyperalgesic responses were measured as latency time (LT) to a thermal stimulus. PK/PD modelling of the antinociceptive response was performed using the population approach with NONMEM VI.

Results:

A two-compartment model described the plasma disposition. A first-order model, including lag time and decreased relative bioavailability as a function of the dose, described the absorption process. The response model was: LT=LT₀/(1 +MED). LT₀ is the baseline response, and MED represents the level of inflammatory mediators. The time course of MED was assumed to be equivalent to the predicted profile of COX-2 activity and was modelled according to an indirect response model with a time variant synthesis rate. Drug effects were described as a reversible inhibition of the COX-2 activity. The in vivo estimate of the dissociation equilibrium constant of the COX-2-lumiracoxib complex was 0.24 µg·mL⁻¹.

Conclusions:

The model developed appropriately described the time course of pharmacological responses to lumiracoxib, in terms of its mechanism of action and pharmacokinetics.     

A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders

Innes AM, Boycott KM, Puffenberger EG, Redl D, MacDonald IM, Chudley AE, Beaulieu C, Perrier R, Gillan T, Wade A, Parboosingh JS. A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders. Bardet‐Biedl syndrome (BBS) is a multisystem genetically heterogeneous disorder, the clinical features of which are largely the consequence of ciliary dysfunction. BBS is typically inherited in an autosomal recessive fashion, and mutations in at least 14 genes have been identified. Here, we report the identification of a founder mutation in the BBS2 gene as the cause for the increased incidence of this developmental disorder in the Hutterite population. To ascertain the Hutterite BBS locus, we performed a genome‐wide single nucleotide polymorphism (SNP) analysis on a single patient and his three unaffected siblings from a Hutterite family. The analysis identified two large SNP blocks that were homozygous in the patient but not in his unaffected siblings, one of these regions contained the BBS2 gene. Sequence analysis and subsequent RNA studies identified and confirmed a novel splice site mutation, c.472‐2A>G, in BBS2. This mutation was also found in homozygous form in three subsequently studied Hutterite BBS patients from two different leuts, confirming that this is a founder mutation in the Hutterite population. Further studies are required to determine the frequency of this mutation and its role, if any, in the expression of other ciliopathies in this population.     

Travel-Associated Dengue Infections in the United States, 1996 to 2005

Background. As the incidence of dengue increases globally, US travelers to endemic areas may be at an increased risk of travel-associated dengue.
Methods. Data from the US Centers for Disease Control and Prevention's laboratory-based Passive Dengue Surveillance System (PDSS) were used to describe trends in travel-associated dengue reported from January 1, 1996 to December 31, 2005. The PDSS relies on provider-initiated requests for diagnostic testing of serum samples via state health departments. A case of travel-associated dengue was defined as a laboratory-positive dengue infection in a resident of the 50 US states and the District of Columbia who had been in a dengue-endemic area within 14 days before symptom onset. Dengue infection was confirmed by serologic and virologic techniques.
Results. One thousand one hundred and ninety-six suspected travel-associated dengue cases were reported—334 (28%) were laboratory-positive, 597 (50%) were laboratory-negative, and 265 (22%) were laboratory-indeterminate. The incidence of laboratory-positive cases varied from 1996 to 2005, but had an overall increase with no significant trend (53.5 to 121.3 per 10⁸ US travelers, p = 0.36). The most commonly visited regions were the Caribbean, Mexico and Central America, and Asia. The median age of laboratory-positive cases was 37 years (range: <1 to 75 y) and 166 (50%) were male. Of the 334 laboratory-positive cases, 41 (12%) were hospitalized, and 2 (1%) died.
Conclusions. Residents of the US traveling to dengue-endemic regions are at risk of dengue infection and need to be instructed on appropriate prevention measures prior to travel. Especially in light of the potential transmissibility of dengue virus via blood transfusion, consistent reporting of travel-associated dengue infections is essential.     

Assessing the interest to participate in a dengue vaccine efficacy trial among residents of Puerto Rico

Dengue, endemic in Puerto Rico, is a major public health problem. Vaccines are thought the best means to prevent dengue because vector control alone has been largely ineffective. We implemented qualitative studies in 2006 and 2010 to determine the acceptability of conducting placebo-controlled dengue vaccine efficacy trials in Puerto Rican children. Key informant interviews and focus groups with parents and children were conducted in municipalities with high dengue incidence. We used structured open-ended questions to determine motivators and attitudes regarding vaccine trial participation. Knowledge about dengue risk and prevention, and knowledge, attitudes, and beliefs regarding vaccines and vaccine trials were assessed. Using grounded theory, we conducted content analysis and established categories and sub-categories of participant responses. All participants were knowledgeable about dengue prevention and perceived children as most affected age groups. Participants were aware of vaccines benefits and they thought a vaccine could prevent dengue. However, most would not allow their children to participate in a placebo-controlled vaccine trial. Barriers included lack of trust in new vaccines and vaccine trial procedures; fear of developing dengue or side effects from the vaccine and lack of information about candidate dengue vaccines. Participants thought information, including results of previous trials might overcome barriers to participation. Motivators for participation were altruism, protection from dengue, free medical attention, and compensation for transportation and participation. Parents would consider children participation if accurate vaccine trial information is provided.     

The contribution of psychological distress to socio-economic differences in cause-specific mortality: a population-based follow-up of 28 years

Background  

Psychological factors associated with low social status have been proposed as one possible explanation for the socio-economic gradient in health. The aim of this study is to explore whether different indicators of psychological distress contribute to socio-economic differences in cause-specific mortality.     

OUR EXPERIENCE WITH DIAGNOSTIC AND THERAPEUTIC CHOLEDOCHOSCOPY

Flexible choledochoscope was used in 16 patients undergoing common bile duct (CBD) exploration for suspected stones. Stones were found in the CBD in 4 patients in whom introperative cholangiogram was normal. T-tube cholangiogram done between the 10th and 14th postoperative days was normal in all 16 patients. None of the patients had symptoms suggestive of retained stones during follow-up ranging from 6 to 19 months. We feel that the use of choledochoscopy in patients undergoing CBD exploration will help reduce the incidence of retained stones.KEY WORDS: Cholangiography, Choledocholithiasis, Choledochoscopy