Anatomical Variations of the Venous Drainage from the Left Adrenal Gland: An Anatomical Study

Background

For radiologists, the venous drainage of adrenal glands is a key to the technique of selective adrenal venous sampling. For endocrine surgeons, it is key to adrenalectomy for carcinoma and pheochromocytoma. This study aims to demonstrate direct anastomosis between the left adrenal vein, the diaphragmatic circulation and the azygos system. Anatomical textbooks only offer very little information concerning the left adrenal vein (LAV) and its potential anastomosis with the reno-lumbo-azygo trunk (RLAT) and the diaphragmatic circulation.

Methods

Between November 2014 and October 2015 in the LADAF (French Alps Anatomy Laboratory), we dissected 44 formalin-fixed adult cadavers.

Results

We found no direct anastomosis between the left adrenal vein and the reno-azygo-lumbar trunk and two anastomoses (4.5%) between the adrenal capsular vein and azygos system. A lumbo-azygo trunk has been found 38 times (86.3%), drained 35 times (79.5%) into the left renal vein and 3 times (6.8%) into the left genital vein. An inferior phrenic vein ending into an adrenal vein was highlighted in all cases, 6 times (13.7%) in a double adrenal vein and 38 times (86.3%) in a single one.

Conclusions

No connections have been found between left adrenal vein and the RLAT, and frequency of the IPV is discordant with the literature. However, our findings concerning the capsular vessels’ anastomosis with the azygos system, inferior diaphragmatic flow and double adrenal vein could have two clinical applications: Firstly, the ligation of the adrenal vein solely is not enough to entirely interrupt the adrenal vein drainage, and secondly, sampling of hormones in the LAV could be underestimated because of the risk of dilution.

     

Comparison of the pharmacokinetics of diazepam after single and subchronic doses

Summary In seven healthy male volunteers the effects of the pattern of dosing on the pharmacokinetics of diazepam have been studied. A cross-over design was employed that consisted of three parts: a single intravenous dose (0.1 mg/kg), and oral dosing (10 mg/day) for six days followed by an intravenous bolus (0.1 mg/kg) on the seventh day, followed by re-examination of a single intravenous dose after diazepam (D) and its major metabolite desmethyldiazepam (DD) had been completely eliminated. Plasma levels of D and DD were monitored by a specific, sensitive GLC-method. In younger patients (n=5, age 29 – 35 years) the elimination half-life, T_{1/2 ()}, of D was 33.9±10.6 h (mean±S.D.) after the single dose. The control study gave an almost identical result (35.7±12.1). After subchronic dosage in all patients T_{1/2 ()} showed a modest but significant prolongation (paired t-test p<0.01) to 52.9±17.4 h. It was caused by a significant decrease (p=0.016) in total plasma clearance ( ), from 26.0±10.8 ml/min to 18.2±7.0 ml/min. Older patients (age 43–60 years) showed the same phenomenon. Blood/plasma ratios remained constant indicating no change in protein binding. Biliary excretion of D was measured in five patients with a T-tube. Only negligible amounts (0.3–0.4%) of administered D were excreted within 3 days after subchronic dosage, which demonstrates a lack of enterohepatic cycling of D. After multiple administration of D, there was accumulation of DD to levels approximately five times higher than after a single dose. The possibility that the slower elimination of D after subchronic treatment might be caused by DD was also supported by experiments in dogs and rabbits. After pretreating rabbits with DD and maintaining a high DD plasma level, there was prolongation of T_{1/2 ()} from 2.7 h to 5.2 h, with a corresponding decrease of from 101.6 ml/min to 23.4 ml/min. Similar results were obtained in dogs. It is concluded that the disposition of D is altered by subchronic use and may be regulated by the plasma DD concentration.The results were presented in part at the 6th International Congress of Pharmacology, Helsinki, 1975     

Oral tyramine pressor test and the safety of monoamine oxidase inhibitor drugs: comparison of brofaromine and tranylcypromine in healthy subjects

The pressor effect of orally administered tyramine (TYR) has been evaluated in 124 tests of 49 healthy unmedicated volunteers, in 99 tests of 29 subjects treated with the reversible selective monoamine oxidase (MAO) A inhibitor brofaromine (BROF), and in 73 tests of 12 subjects treated with tranylcypromine (TCP). In unmedicated subjects, pressor doses of TYR to raise systolic blood pressure (BP) by 30 mm Hg (PD30) ranged between 200 and 800 mg of TYR. There was no correlation of PD30 with sex, age, or weight. In repeated tests, the intraindividual coefficient of variation of the PD30 (+/- SD) was 10 +/- 9%. During treatment for 8 to 16 days with the two MAO inhibitors (MAOIs) BROF and TCP, seven-fold and 56-fold increases of TYR pressor sensitivity were estimated. A significant correlation was found between the individual PD30 before and during MAO inhibition with BROF. Cheese with a pressor content equal to the PD30 of TYR raised the systolic BP in only three of 10 volunteers during BROF inconsistently by not more than 20 mm. Therefore, the probability of "cheese reactions" during treatment with this reversible MAOI seems to be small. For complete normalization of oral pressor responsiveness, delays of 8 and 30 days after the last doses of BROF and TCP, respectively, are needed. The total incidence of systolic BP elevations by more than 60 mm Hg was 13% in a total of 296 oral tests given to 49 subjects. This incidence of easily controllable hypertensive reactions is outweighed by the importance of the test as predictor of clinical risks for drugs with TYR potentiating effects.     

SARS-CoV-2 Omicron Variant,Lineage BA.1, Is Associated with Lower Viral Load in Nasopharyngeal Samples Compared to Delta Variant

Objectives: High viral load in upper respiratory tract specimens observed for Delta cases might contribute to its increased infectivity compared to the other variant. However, it is not yet documented if the Omicron variant’s enhanced infectivity is also related to a higher viral load. Our aim was to determine if the Omicron variant’s spread is also related to higher viral loads compared to the Delta variant. Methods: Nasopharyngeal swabs, 129 (Omicron) and 85 (Delta), from Health Care Workers were collected during December 2021 at the University Hospital of Lyon, France. Cycle threshold (Ct) for the RdRp target of cobas^® 6800 SARS-CoV-2 assay was used as a proxy to evaluate SARS-CoV-2 viral load. Variant identification was performed using a screening panel and confirmed by whole genome sequencing. Results: Herein, we showed that the RT-PCR Ct values in Health Care Workers sampled within 5 days after symptom onset were significantly higher for Omicron cases than Delta cases (21.7 for Delta variant and 23.8 for Omicron variant, p = 0.008). This difference was also observed regarding patient with complete vaccination. Conclusions: This result supports the studies showing that the increased transmissibility of Omicron is related to other mechanisms than higher virus excretion.     

The Role of GDF-15 in Heart Failure Patients With Chronic Kidney Disease

Background

Growth differentiation factor-15 (GDF-15) is a stress-inducible cytokine and member of the transforming growth factor-β cytokine superfamily that refines prognostic assessment in subgroups of patients with heart failure (HF). We evaluated its role in HF patients with chronic kidney disease (CKD, estimated glomerular filtration rate <60 mL/min/1.73 m²).

Hydroxyapatite porous coating and the osteointegration of the total hip replacement

Introduction The main purpose of this study is to evaluate the efficacy of the plasma sprayed, combined porous titanium alloy/HA coating in promoting bony ingrowth and mechanical stabilization of total hip implants. The performance of the titanium alloy/HA type coated hip prostheses and the one of the same shape but without any coating, is compared in this paper. Material and methods The implants were manufactured from titanium alloy VT-6 (ASTM F-136). The hip stems utilized in the control group were identical to those subsequently coated. The coating consists of a plasma deposited first layer of porous titanium alloy (TiAl₆V₄), similar in composition to the forged substrate and a plasma deposited second layer of oversprayed hydroxyapatite, Ca₁₀ (PO₄)₆ (OH) ₂. Coating is located in the critical area of the hip stems, where high fixation interface strength is desired, i.e. in the proximal area of the stem where the highest stresses occur. The porous titanium alloy/hydroxyapatite (HA) coated femoral stems were implanted in 50 patients. The results were compared with a control group of 50 patients with the same type of endoprosthesis, but without the porous titanium alloy/HA coating. Both groups of patients were operated on and evaluated by the same orthopedic surgeons with a mean follow up of 11.4 years in the HA group and 10.6 years in the control group. Results HHS in the control group was preoperatively 35.5 points (range 26–49) and 85.1 points (range 54–100) in the time of the last control. HHS in the HA group was preoperatively 34.1 points (range 27–56) and 94.4 points (range 89–100) in the time of the last control. In 28 cases (56%) of the control group a range of translucencies were obvious. These translucent lines, however, did not appear with any of the patients in the coated implant group except one infection stem migration. Conclusion Experience with the HA-type coated hip implants demonstrates substantially higher degree and quality of osteointegration in the porous titanium alloy/HA type implants.     

Surveillance of adverse fetal effects of medications (SAFE-Med): Findings from the International Clearinghouse of Birth Defects Surveillance and Research

To evaluate whether the routinely collected data in birth defect registries could be used to assess association between medications and risk for congenital anomalies an “exposed case-only” design was performed.Twelve registries provided 18,131 cases exposed to a medication during the first trimester of pregnancy and with at least one major malformation. Odds ratios for malformations associated with maternal use of selected medications were computed.Among seven most commonly used medications very few significant associations with malformations were identified. Among fourteen potentially teratogenic medications several strong associations were found, including valproic acid with spina bifida, and insulin (as proxy for diabetes) with several types of cardiac defects.Finding known associations provides assurance on the validity of this approach, whereas identifying new associations provides a signal to be followed by confirmatory studies. Through this activity, international networks of birth defect registries can contribute with limited resources to post-marketing surveillance of the teratogenicity of medications.     

Higher toxicity with 42 Gy in 10 fractions as a total dose for 3D-conformal accelerated partial breast irradiation: results from a dose escalation phase II trial

ABSTRACT: OBJECTIVE: Recent recommendations regarding indications of accelerated partial breast irradiation (APBI) have been put forward for selected breast cancer (BC) patients. However, some treatment planning parameters, such as total dose, are not yet well defined. The Institut Gustave Roussy has initiated a dose escalation trial at the 40 Gy/10 fractions/5 days and at a further step of total dose (TD) of 42 Gy/10 fractions/ 5 days. Here, we report early results of the latest step compared with the 40 Gy dose level.Methods and materialsFrom October 2007 to March 2010, a total of 48 pT1N0 BC patients were enrolled within this clinical trial: 17 patients at a TD of 42 Gy/10f/5d and 31 at a TD of 40 Gy/10f/5d. Median follow-up was 19 months (min-max, 12--26). All the patients were treated by APBI using a technique with 2 minitangents and an "enface" electrons delivering 20% of the total dose. Toxicities were systematically assessed at 1; 2; 6 months and then every 6 months. RESULTS: Patients' recruitment of 42 Gy step was ended owing to persistent grade 3 toxicity 6 months after APBI completion (n = 1). Early toxicities were statistically higher after a total dose of 42 Gy regarding grade [GREATER-THAN OR EQUAL TO]2 dry (p = 0.01) and moist (p = 0.05) skin desquamation. Breast pain was also statistically higher in the 42 Gy step compared to 40 Gy step (p = 0.02). Other late toxicities (grade [GREATER-THAN OR EQUAL TO]2 fibrosis and telangectasia) were not statistically different between 42 Gy and 40 Gy. CONCLUSIONS: Early toxicities were more severe and higher rates of late toxicities were observed after 42 Gy/10 fractions/5 days when compared to 40 Gy/10 fractions/5 days. This data suggest that 40 Gy/10 fractions/ 5 days could potentially be the maximum tolerance for PBI although longer follow-up is warranted to better assess late toxicities.