The common 'thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia

Mild hyperhomocysteinaemia is a major risk factor for vascular disease and neural tube defects (NTDs), conferring an approximately three-fold relative risk for each condition. It has several possible causes: heterozygosity for rare loss of function mutations in the genes for 5,10-methylene tetrahydrofolate reductase (MTHFR) or cystathionine-&bgr;-synthase (CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or homozygosity for a common 'thermolabile' mutation in the MTHFR gene which has also been associated with vascular disease and NTDs. We quantified the contribution of the thermolabile mutation to the hyperhomocysteinaemic phenotype in a working male population (625 individuals). Serum folate and vitamin B12 concentrations were also measured and their relationship with homocysteine status and MTHFR genotype assessed. The homozygous thermolabile genotype occurred in 48.4, 35.5, and 23.4% for the top 5, 10 and 20% of individuals repectively) ranked by plasma homocysteine levels, compared with a frequency of 11.5% in the study population as a whole establishing that the mutation is a major determinant of homocystein levels at the upper end of the range. Serum folate concentrations also varied with genotype, being lowest in thermolabile homozygotes. The MTHFR thermolabile genotype should be considered when population studies are designed to determine the effective homocysteine-lowering dose of dietary folate supplements, and when prophylactic doses of folate are recommended for individuals.      

Retroperitoneal approach in laparoscopic adrenalectomy

Recently, the retroperitoneal laparoscopic approach has been described as advantageous in avoiding the respiratory and hemodynamic effects of CO₂ pneumoperitoneum and giving direct access without the need to move abdominal organs. Forty-two laparoscopic adrenalectomies (LpA) were performed in 36 patients with a variety of adrenal disorders, including 9 patients with nonfunctioning tumors, 11 patients with aldosterone adenoma, 10 patients with Cushing's adenoma, and 6 patients with Cushing's disease. Twenty-two adrenalectomies were performed using the transperitoneal approach (TLpA), and 20 via the retroperitoneoscopic approach (RLpA). Arterial blood samples, mean arterial pressure, heart rate, and clinical parameters were evaluated. At the end of the operation, the PaCO₂, PetCO₂, and base deficit all increased significantly in both retroperitoneal and transperitoneal CO₂ insufflation compared with basal values. Arterial pH decreased significantly in both TLpA and RLpA groups. All clinical parameters evaluated (operation time, analgesic dosing requirements, hospital stay, and the days until return to normal activity) were similar in the TLpA and RLpA approaches. Two patients in the TLpA (10.5%) group and two patients in the RLpA (10%) group needed conversion to open surgery. This study shows the safety and efficacy of laparoscopic adrenalectomy via the transperitoneal or retroperitoneal route in patients with a variety of adrenal disorders. The retroperitoneoscopic approach could be the primary choice in patients with previous abdominal surgery. Received: 3 April 1997/Accepted: 26 August 1997     

Nocturnal Pulse Event Frequency Is Reduced in Multiple System Atrophy

Risk of sudden death in multiple system atrophy (MSA) is greatest during sleep with unknown mechanisms. We compared nocturnal pulse event frequency in 46 MSA patients and age-/sex-matched controls undergoing overnight pulse oximetry. Nocturnal oxyhemoglobin desaturation indices and pulse event indices (PEIs) were recorded, and relationships between pulse oximetry variables and survival were analyzed. MSA patients had lower PEI (3.1 ± 5.3 vs. 12.8 ± 10.8, p < 0.001) despite greater hypoxic burden and similar frequency of respiratory events. Nocturnal pulse events were not associated with severity of daytime autonomic failure. Two MSA patients had suspected sudden death, both with severely reduced PEI. MSA patients have fewer nocturnal pulse events compared with controls, despite similar respiratory event frequency, suggesting abnormal cardiac responses to sleep-disordered breathing. Whether this contributes to sudden death in MSA requires further study. ANN NEUROL 2023;93:205–212