Control of Diabetic Gustatory Hyperhidrosis With Topical 20% Aluminum Chloride Hexahydrate.

Diabetic gustatory hyperhidrosis is a late sequela of diabetes and can have profound consequences. We report a case of diabetic gustatory hyperhidrosis controlled with topical aluminum chloride hexahydrate and support this as a first-line treatment. Aluminum chloride hexahydrate is a safe, effective, inexpensive and commercially available treatment.

Collateral circulation of the femoral and genicular systems in human lower limbs is highly uncommon.

The descending branch of the lateral circumflex artery is a septocutaneous vessel that is vital for free and pedicle thigh flap transfer surgeries when repairing tissue defects. It also forms an anastomosis with the superior lateral genicular artery to create a collateral pathway for circumventing occlusions in the superficial femoral artery (SFA). Many anatomical texts and atlases imply the persistence of this anastomosis. However, previous studies indicate variability in the source of the arteries that form the anastomosis, and have reported cases where an anastomosis does not exist. We hypothesized that variations from the conventional accepted pattern can be predicted by comparisons of arterial diameters, and that unconventional anastomoses may be present to facilitate collateral circulation to the limb. Fifty-one limbs were dissected and analyzed to establish the source of the descending branch of the lateral circumflex artery, classify the types of anastomoses, and compare the diameters of the descending branch of the lateral circumflex artery, the SFA and the profunda femoris artery to the common femoral artery (CFA). Vessel diameters were normalized to the diameter of the CFA to allow comparison of limbs from both sexes and to minimize the effects of cadaver size on correlating vessel size to the presence or absence of collateral circuits. We report that 62.7% of limbs (32/51) had typical branching patterns; however, only 27.4% of limbs (14/51) had any anastomosis to connect the proximal and distal regions of the thigh. Importantly, the SFA had a wider relative diameter in limbs without anastomoses than in limbs that had normal anastomoses, perhaps precluding the formation of a collateral pathway. Overall, collateral circulation of the lower limb was highly uncommon, in contrast to information inferred from anatomical texts. This study suggests the need for more thorough procedures for determining viable anastomoses prior to thigh flap surgeries to ensure flap survival.

A Three-Dimensional Print Model of the Pterygopalatine Fossa Significantly Enhances the Learning Experience.

The pterygopalatine fossa (PPF) is a bilateral space deep within the skull that serves as a major neurovascular junction. However, its small volume and poor accessibility make it a difficult space to comprehend using two-dimensional illustrations and cadaveric dissections. A three-dimensional (3D) printed model of the PPF was developed as a visual and kinesthetic learning tool for completely visualizing the fossa, its boundaries, its communicating channels, and its neurovascular structures. The model was evaluated by analyzing student performance on pre- and post-quizzes and a student satisfaction survey based on the five-point Likert scale. The first cohort comprised of 88 students who had never before studied the PPF. The second cohort consisted of 30 students who were previously taught the PPF. Each cohort was randomly divided into a control group who were provided with a half skull and an intervention group that were provided with the 3D printed model. The intervention group performed significantly better on the post-quiz as compared to the control group in cohort I (P = 0.001); while not significant, it also improved learning in cohort II students (P = 0.124). Satisfaction surveys indicated that the intervention group found the 3D printed model to be significantly more useful (P < 0.05) as compared to the half skull used by the control group. Importantly, the effect sizes for cohorts I and II (0.504 and 0.581, respectively) validated the statistical results. Together, this study highlights the importance of 3D printed models as teaching tools in anatomy education.

IGF-1R inhibition induces schedule-dependent sensitization of human melanoma to temozolomide.

Prior studies implicate type 1 IGF receptor (IGF-1R) in mediating chemo-resistance. Here, we investigated whether IGF-1R influences response to temozolomide (TMZ), which generates DNA adducts that are removed by O6-methylguanine-DNA methyltransferase (MGMT), or persist causing replication-associated double-strand breaks (DSBs). Initial assessment in 10 melanoma cell lines revealed that TMZ resistance correlated with MGMT expression (r = 0.79, p = 0.009), and in MGMT-proficient cell lines, with phospho-IGF-1R (r = 0.81, p = 0.038), suggesting that TMZ resistance associates with IGF-1R activation. Next, effects of IGF-1R inhibitors (IGF-1Ri) AZ3801 and linsitinib (OSI-906) were tested on TMZ-sensitivity, cell cycle progression and DSB induction. IGF-1Ri sensitized BRAF wild-type and mutant melanoma cells to TMZ in vitro, an effect that was independent of MGMT. Cells harboring wild-type p53 were more sensitive to IGF-1Ri, and showed schedule-dependent chemo-sensitization that was most effective when IGF-1Ri followed TMZ. This sequence sensitized to clinically-achievable TMZ concentrations and enhanced TMZ-induced apoptosis. Simultaneous or prior IGF-1Ri caused less effective chemo-sensitization, associated with increased G1 population and reduced accumulation of TMZ-induced DSBs. Clinically relevant sequential (TMZ → IGF-1Ri) treatment was tested in mice bearing A375M (V600E BRAF, wild-type p53) melanoma xenografts, achieving peak plasma/tumor IGF-1Ri levels comparable to clinical Cmax, and inducing extensive intratumoral apoptosis. TMZ or IGF-1Ri caused minor inhibition of tumor growth (gradient reduction 13%, 25% respectively), while combination treatment caused supra-additive growth delay (72%) that was significantly different from control (p < 0.01), TMZ (p < 0.01) and IGF-1Ri (p < 0.05) groups. These data highlight the importance of scheduling when combining IGF-1Ri and other targeted agents with drugs that induce replication-associated DNA damage.