Spinal and peripheral bone mineral densities in acromegaly: the effects of excess growth hormone and hypogonadism

STUDY OBJECTIVE: To measure spinal and peripheral bone mineral densities in patients with acromegaly. DESIGN: Retrospective study. SETTING: Tertiary care center. SUBJECTS: Twenty-four patients with acromegaly and 24 case controls. Seventeen patients (12 eugonadal and 5 hypogonadal) had "active" disease as indicated by elevated plasma concentrations of growth hormone or somatomedin C or both at the time of the study. Seven patients (all hypogonadal) had inactive disease by these criteria. MEASUREMENTS AND MAIN RESULTS: Bone mineral was measured by single photon absorptiometry of the forearm and dual photon absorptiometry of the spine. The forearm bone mineral content of patients with active disease, regardless of gonadal status, was significantly higher than that of normal subjects (P less than 0.001) or of patients with inactive disease (P less than 0.001). The disease "activity" (17.2 +/- 3.7; CI, 9.5 to 24.9) and the sex of the patient (female, -16.6 +/- 3.4; CI, -23.7 to -9.5) were the only independent predictors of forearm measurements. Vertebral bone densities were lower in acromegalic patients than in normal subjects (P less than 0.001). Vertebral values were correlated with the gonadal status of the patients (hypogonadism, -0.126 +/- 0.056; CI, -0.244 to -0.009) and with serum calcium concentrations (0.592 +/- 0.274; CI, 0.032 to 1.153) but not with acromegalic activity. In 13 patients, forearm bone was measured before and after treatment (mean duration of follow-up, 3.4 years). Patients with persistently elevated, plasma somatomedin C concentrations at the end of the study period showed a mean annual increase of 1.5% in forearm measurements during the period of observation, whereas patients with normal concentrations showed a mean annual decrease of 1.0% (P less than 0.01 for the difference between the groups). The percent change in forearm bone mineral content per year (y) was highly correlated with residual somatomedin C activity (x): y = 2.023x - 2.75; r = 0.665. CONCLUSIONS: Forearm and vertebral bone mineral measurements change in opposite directions in acromegaly. The high forearm values are attributable to the growth-promoting action of growth hormone and somatomedin C, whereas low vertebral values are associated with hypogonadism.     

Histoid leprosy: a rare exuberant case

Leprosy is a neglected disease. We point up the need of recognizing the unusual clinical presentations of the disease in order to make early diagnosis and proper treatment possible, and break the transmission chain. The authors report a rare type of multibacillary leprosy: histoid leprosy and present images of numerous well-circumscribed indurated papules and nodules distributed throughout the entire body.     

Permeability of the hard tissue bridge formed after pulpotomy with calcium hydroxide: a histologic study.

Analysis of these results shows that complete hard tissue bridges, aside from occurring with great frequency, produce a satisfactory protection to the pulp. In a case in which the barrier is incomplete, some future clinical problems may result as an incomplete barrier does not offer adequate protection as shown by the chronic inflammatory reaction in the remaining pulp tissue.     

Aspartic proteinases of Candida spp.: role in pathogenicity and antifungal resistance

Fungal infections represent a serious health risk as they are particularly prevalent in immunocompromised individuals. Candida spp. pathogenicity depends on several factors and secreted aspartic proteinases (Sap) are considered one of the most critical factors as they are associated with adhesion, invasion and tissue damage. The production of proteinases is encoded by a family of 10 genes known as SAP, which are distributed differently among the species. The expression of these genes may be influenced by environmental conditions, which generally result in a higher fungal invasive potential. Non‐pathogenic Candida spp. usually have fewer SAP genes, which are not necessarily expressed in the genome. Exposure to subinhibitory concentrations of antifungal agents promotes the development of resistant strains with an increased expression of SAP genes. In general, Candida spp. isolates that are resistant to antifungals show a higher secretion of Sap than the susceptible isolates. The relationship between Sap secretion and the susceptibility profile of the isolates is of great interest, although the role of SAPs in the development of resistance to antifungal agents remains still unclear. This review is the first one to address these issues.     

Abnormal cellular energy and phospholipid metabolism in the left dorsolateral prefrontal cortex of medication-free individuals with bipolar disorder: an in vivo1H MRS study

Objectives:  While the pathophysiology of bipolar disorder (BD) remains to be elucidated, postmortem and neuroimaging studies have suggested that abnormalities in the dorsolateral prefrontal cortex (DLPFC) are implicated. We compared the levels of specific brain chemicals of interest measured with proton magnetic resonance spectroscopy (¹H MRS) in medication-free BD subjects and age- and gender-matched healthy controls. We hypothesized that BD subjects would present abnormal cellular metabolism within the DLPFC, as reflected by lower N -acetyl-aspartate (NAA) and creatine + phosphocreatine (Cr + PCr).
Methods:  Thirty-two medication-free BD subjects (33.8 ± 10.2 years) and 32 matched controls (33.8 ± 9.0 years) underwent a short echo-time (TE = 30 ms) ¹H MRS. An 8-cm³ single voxel was placed in the left DLPFC, and individual concentrations of NAA, Cr + PCr, choline-containing compounds (GPC + PC), myo -inositol, and glutamate were obtained, using the water signal as an internal reference.
Results:  BD subjects had lower Cr + PCr [ F _(1,62) = 5.85; p = 0.018; one-way analysis of variance (ANOVA)] and lower GPC + PC [ F _(1,62) = 5.79; p = 0.019; one-way ANOVA] levels in the left DLPFC. No significant differences were observed for other brain metabolites.
Conclusions:  These findings provide further evidence that the pathophysiology of BD involves impairment in the DLPFC. Our findings can be interpreted as evidence for reduced cellular energy and phospholipid metabolism, consistent with the hypothesis of mitochondrial dysfunction in BD.     

Analysis of pancreatic adenocarcinoma tumor staging and resection according to previous body mass index and diabetes duration.

BACKGROUND/AIMS: Obesity and diabetes mellitus (DM) are associated with pancreatic cancer. The present study evaluated tumor staging and resection of pancreatic adenocarcinoma (PaC) according to previous Body Mass Index (BMI), BMI on admission and DM duration. METHODS: A retrospective analysis of 151 consecutive patients with PaC was performed: 73 were evaluated according to BMI preceding tumor-related weight loss and BMI on admission; 118 according to DM diagnosis; and 38 were assessed according to DM duration (less than 1 year [recent-onset] versus more than 2 years [long-standing]). RESULTS: There was no difference in the prevalence of tumor stage III or IV between previously normal weight and overweight/obese patients (56 vs. 42%, NS). Tumor resection rate was higher in previously obese than in previously lean patients (58 vs. 24%, p < 0.05). Tumor staging and resection were similar between normal weight and overweight/obese patients considering BMI on admission and diagnosis of DM. Weight loss was more pronounced in diabetic than in non-diabetic patients (21.7 vs. 13.3%, p < 0.01). Tumor staging and resection were similar between recent-onset and long-standing diabetic patients. CONCLUSION: Tumor resection rate was lower in previously normal weight patients. Diabetics lost more weight than non-diabetic patients. Neither BMI on admission nor the presence of DM nor DM duration influenced tumor staging or resection in PaC patients.     

Hansen's disease in a general hospital: uncommon presentations and delay in diagnosis

Background  The question was raised as to why 'obvious' signs of leprosy, Hansen's disease (HD), are often missed by medical doctors working in a HD endemic area.
Methods  This study describes a small sample of patients who were diagnosed with HD during their hospital admission and not before. The discussion is whether the typical early signs and symptoms of HD are just not recognized, or whether unusual presentations confuse the attending physician.
Results  A total of 23 HD patients were hospitalized during the study period, of which 6 (26%) were only diagnosed with HD during their admission. All were classified as lepromatous leprosy (LL) with a history of signs and symptoms of HD. In nearly all patients, a suspicion of HD might have been raised earlier if a careful history and dermato-neurological examination had been done.
Conclusions  Multibacillary (MB) HD, especially close to the lepromatous end of the spectrum, may mimic other diseases, and the patient can not be diagnosed without a biopsy or a slit skin smear examination. Clinicians working in a HD endemic area (Rio de Janeiro) do not always include HD in their differential diagnosis, especially when the clinical presentation is unusual. HD should be considered in all patients with skin lesions not responding to treatment, especially when they have neurological deficits, and live or have lived in an HD endemic area. Due to the increase in global travel and immigration, doctors in low endemic areas need to consider HD as a possible diagnosis.

Conflicts of interest

None declared     

Internally quenched fluorogenic substrates for angiotensin I-converting enzyme.

OBJECTIVE: Development of internally quenched fluorogenic substrates for sensitive and continuous assays of angiotensin I-converting enzyme (ACE). DESIGN: We synthesized internally quenched fluorogenic bradykinin-related peptides introducing Abz (ortho-aminobenzoic acid) and EDDnp (N-[2,4-dinitrophenyl]-ethylenediamine) at their N- and C-terminal groups, respectively, and these were assayed as ACE substrates. We examined two series of peptides, Abz-GFSPFRX-EDDnp and Abz-GFSPFXQ-EDDnp (X, various amino acids). METHODS: Hydrolysis of the fluorogenic substrates by ACE was followed by continuous recording of the rising fluorescence (lambda(em) = 420 nm and lambda(ex) = 320 nm). The peptides were obtained by solid-phase synthesis or by classical solution methods. RESULTS: Despite of the blocked C-terminal sequences, the internally quenched bradykinin-related peptides were hydrolysed by ACE. The best substrates for plasma guinea pig ACE were Abz-GFSPFRA-EDDnp and Abz-GFSPFFQ-EDDnp, in which the fluorescence appeared after the first cleavage that occurred at R-A and F-Q bond, respectively. This ACE activity was sensitive to NaCl concentration and the optimum pH is greater than 8.0. Measurements of ACE activity with Hip-His-Leu and Abz-GFSPFFQ-EDDnp in the serum of 20 healthy patients correlated closely (r = 0.959). Complete inhibition of the hydrolysis of Abz-GFSPFFQ-EDDnp by human serum was observed with captopril and lisinopril. CONCLUSIONS: We describe internally quenched fluorogenic substrates for ACE devoid of free C-terminal carboxyl group. They are convenient tools for ACE studies as they permit continuous fluorimetric measurements of the enzymatic activity, even in human serum.