Hypercalcemia After Cosmetic Oil Injections: Unraveling Etiology,Pathogenesis, and Severity

Intramuscular injections of paraffin oil can cause foreign body granuloma formation and hypercalcemia. Macrophages with the ability to produce high levels of 1,25(OH)₂D₃ may induce the mineral disturbance, but no major series of patients have been published to date. Here, medical history, physical evaluation, biochemical, and urinary analysis for calcium homeostasis were obtained from 88 males, who 6 years previously had injected paraffin or synthol oil into skeletal muscle. Moreover, granuloma tissue from three men was cultured for 48 hours ex vivo to determine 1,25(OH)₂D₃ production supported by qPCR and immunohistochemistry of vitamin D metabolism and immune cell populations after treatment with 14 different drugs. The 88 men were stratified into men with hypercalcemia (34%), whereas normocalcemic men were separated into men with either normal (42%) or suppressed parathyroid hormone (PTH) (24%). All men had high calcium excretion, and nephrolithiasis was found in 48% of hypercalcemic men, 22% of normocalcemic men with normal PTH, and 47% of normocalcemic men with suppressed PTH. Risk factors for developing hypercalcemia were oil volume injected, injection of heated oil, high serum interleukin-2 receptor levels, and high urine calcium. High 1,25(OH)₂D₃/25OHD ratio, calcium excretion, and low PTH was associated with nephrolithiasis. The vitamin D activating enzyme CYP27B1 was markedly expressed in granuloma tissue, and 1,25(OH)₂D₃ was released in concentrations corresponding to 40% to 50% of the production by human kidney specimens. Dexamethasone, ketoconazole, and ciclosporin significantly suppressed granulomatous production of 1,25(OH)₂D₃. In conclusion, this study shows that injection of large oil volumes alters calcium homeostasis and increases the risk of nephrolithiasis. Hypercalciuria is an early sign of disease, and high granulomatous 1,25(OH)₂D₃ production is part of the cause. Prospective clinical trials are needed to determine if ciclosporin, ketoconazole, or other drugs can be used as prednisolone-sparing treatment. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Whiplash injury and oculomotor dysfunctions: clinical–posturographic correlations

Oculomotor dysfunctions are hidden causes of invalidity following whiplash injury. Many patients with whiplash injury grade II present oculomotor dysfunctions related to input disturbances of cervical or vestibular afferents. We used static posturography to investigate 40 consecutive patients with whiplash injury grade II and oculomotor dysfunctions. We demonstrated a relation between length and surface of body sway: the surface value (A) was higher than the length value (L) and this led to an open graph of body sway in the statokinesigram. Oculomotor rehabilitation can resolve the impairment of vestibular function but if therapy is delayed or the patient has been wearing an orthopaedic neck collar, more therapeutic sessions are required. In conclusion, without rehabilitation of the oculomotor muscles other therapies are not sufficient to recover the impairment caused by whiplash injury.     

Genitourinary small cell carcinoma: a retrospective review of treatment and survival patterns at The Ottawa Hospital Regional Cancer Center

OBJECTIVE: To review patients with genitourinary (GU) small cell carcinoma (SCC) treated at a regional cancer centre, as due to its rarity and aggressive nature, GU SCC remains a therapeutic challenge. PATIENTS AND METHODS: The charts of patients managed at a regional cancer centre between 1991 and 2002 for any GU diagnosis were manually reviewed to identify GU SCC. Demographic, staging, treatment and outcome data were extracted. The Veterans Administration small cell lung cancer staging classification of "limited" or "extensive" disease was adapted for SCC of the prostate and bladder (with "limited" defined as disease localized to the true and false pelvis, and "extensive" as disease beyond the pelvis). RESULTS: In all, 555, 858 and 5066 new cases of primary renal, bladder and prostate cancer, respectively, were identified. Of these patients, 22 had GU SCC (12 bladder and 10 prostate; there were no cases of SCC of the kidney). Eight of 12 patients with bladder SCC had limited disease; five of 12 are alive (all with limited disease at diagnosis), and the median survival was 19.8 months. Surviving patients received similar therapy, with transurethral resection of the bladder tumour, platinum-based chemotherapy, etoposide (4-6 cycles), and radical radiotherapy (56-60 Gy). Two of 10 patients with SCC of the prostate had limited-stage disease, but all 10 died, the median survival being 9.5 months. Survival by stage for both types combined was 59 months for limited disease and 8 months for extensive disease. CONCLUSIONS: These results indicate that GU SCC is an aggressive cancer; limited-stage SCC of the bladder or prostate, when treated with platinum/etoposide chemotherapy and radical radiotherapy, has a more favourable outcome than that of extensive GU SCC.     

Phylogenetic and evolutionary analysis of HoBi‐like pestivirus: Insights into origin and dispersal

The HoBi‐like pestivirus (HoBiPeV), currently classified as Pestivirus H species, is a pathogen associated with a broad spectrum of clinical manifestations in ruminants, particularly in cattle. Since HoBiPeV complete genome sequencing data is scarce, in the present study we described five nearly complete new Brazilian HoBiPeV genomes and further perform a more complete genetic and evolutionary characterization with all additional genome sequences available in the GenBank database. Entropy and selection pressure analysis showed the E2 gene, a surface glycoprotein, is the most variable gene, which also displays the greatest number of sites under positive selection. Phylogenetic and Bayesian inference based on complete genome and N^pro gene, respectively, from all HoBiPeV sequences available so far, confirms the existence of three main clades (a, b, and c). The abovementioned analysis suggests that this pestivirus species probably emerged in Asia and spread to different regions including Brazil, where only strains belonging to specific genetic group ‘a’ have been found. The hypothesis of the HoBiPeV introduction in Brazil (between 1,890 and 1,962), formulated based on Bayesian inference, coincides with a period of intensive importation of water buffalo (Bubalus arnee) and indicine cattle (Bos taurus indicus) from Asia to Brazil, suggesting that this could be the origin of the current Brazilian HoBiPeV genetic group ‘a’.     

Penetration and haptenation of p‐phenylenediamine

Although p‐phenylenediamine (PPD) has been recognized as an extreme sensitizer for many years, the exact mechanism of sensitization has not been elucidated yet. Penetration and the ability to bind to proteins are the first two hurdles that an allergen has to overcome to be able to sensitize. This review is an overview of studies regarding PPD penetration through skin (analogues) and studies on the amino acids that are targeted by PPD. To complete this review, the auto‐oxidation and N‐acetylation steps involved in PPD metabolism are described. In summary, under normal hair dyeing exposure conditions, <1% of the applied PPD dose penetrates the skin. The majority (>80%) of PPD that penetrates will be converted into the detoxification products monoacetyl‐PPD and diacetyl‐PPD by the N‐acetyltransferase enzymes. The small amount of PPD that does not become N‐acetylated is susceptible to auto‐oxidation reactions, yielding protein‐reactive PPD derivatives. These derivatives may bind to specific amino acids, and some of the formed adducts might be the complexes responsible for sensitization. However, true in vivo evidence is lacking, and further research to unravel the definite mechanism of sensitization is needed.     

PERSONALITY FEATURES AND DISORDER IN THE SUBJECTS IN THE NEW YORK HIGH-RISK PROJECT

One hundred and seventy-five offspring of parents in two psychiatrically ill groups and of normal controls in the New York High-Risk Project (NYHRP) were assessed for Axis II personality traits and disorders as defined by the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R). These offspring include: subjects at high risk for schizophrenia (HRSz, n = 48), all of whom have a parent with schizophrenic disorder; subjects at high risk for affective disorder (HRAff, n = 40), all of whom have a parent with affective disorder; and subjects at no increased risk for psychiatric illness (NC, n = 87), whose parents are psychiatrically normal. The trained interviewers, who administered a standardized direct interview, were blind to parental clinical status and to previous clinical status of the offspring.

The rates for any personality disorder (PD) ranged from 7% to 20%. Comorbidity between Axis I and Axis II disorders was high for all groups.     

Using others' words: conversational use of reported speech by individuals with aphasia and their communication partners.

Reported speech, wherein one quotes or paraphrases the speech of another, has been studied extensively as a set of linguistic and discourse practices. Researchers agree that reported speech is pervasive, found across languages, and used in diverse contexts. However, to date, there have been no studies of the use of reported speech among individuals with aphasia. Grounded in an interactional sociolinguistic perspective, the study presented here documents and analyzes the use of reported speech by 7 adults with mild to moderately severe aphasia and their routine communication partners. Each of the 7 pairs was videotaped in 4 everyday activities at home or around the community, yielding over 27 hr of conversational interaction for analysis. A coding scheme was developed that identified 5 types of explicitly marked reported speech: direct, indirect, projected, indexed, and undecided. Analysis of the data documented reported speech as a common discourse practice used successfully by the individuals with aphasia and their communication partners. All participants produced reported speech at least once, and across all observations the target pairs produced 400 reported speech episodes (RSEs), 149 by individuals with aphasia and 251 by their communication partners. For all participants, direct and indirect forms were the most prevalent (70% of RSEs). Situated discourse analysis of specific episodes of reported speech used by 3 of the pairs provides detailed portraits of the diverse interactional, referential, social, and discourse functions of reported speech and explores ways that the pairs used reported speech to successfully frame talk despite their ongoing management of aphasia.