Principles of surgery according to the Integral Theory Paradigm (ITP).

A core concept of the Integral Theory System is that "ligaments are for structure; vagina is for function". The vagina and uterus should be conserved. Because the vagina is an organ, its collagen and elastin, which are so necessary for its function, cannot regenerate once they are removed. Removing the uterus involves severing the descending uterine artery, which is the principal blood supply of the proximal part of the uterosacral ligaments (USLs), and so may cause atrophy, which can cause future incontinence problems because of collagen loss after menopause. The diagnostic algorithm guides which of the five pelvic ligaments need repair. Native ligament plication can be adequate for prolapse/symptom cure, but only in premenopausal women. Postmenopausal women are usually collagen deficient and require collagen-creating tapes or wide-bore polyester sutures to restore structural collagen in the ligaments. Of extreme importance, vaginal tissue excision should be avoided, as consequent scarring may cause "tethered vagina syndrome" (TVS). TVS can cause massive uncontrolled urine loss because the scar tissue in the bladder neck area of the vagina can link the more powerful posterior muscles to the anterior, so the posterior urethra wall is forcibly pulled open, when given the signal to close. Instead of vaginal excision, a "concertina" suture technique re-assigns and shrinks excess vaginal tissue to normal anatomy by 6 weeks. In conclusion, the five key surgical principles of the Integral Theory System are: ligaments are for structure, vagina is for function; structure (prolapse) and function (symptoms) are related; repair the structure and you will restore the function; avoid vaginal excision and hysterectomy; create new collagen to reinforce the damaged ligaments.

Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.

Nicotinamide adenine dinucleotide (NAD(+)) is an essential electron transporter in mitochondrial respiration and oxidative phosphorylation. In genomic DNA, NAD(+) also represents the sole substrate for the nuclear repair enzyme, poly(ADP-ribose) polymerase (PARP) and the sirtuin family of NAD-dependent histone deacetylases. Age associated increases in oxidative nuclear damage have been associated with PARP-mediated NAD(+) depletion and loss of SIRT1 activity in rodents. In this study, we further investigated whether these same associations were present in aging human tissue. Human pelvic skin samples were obtained from consenting patients aged between 15-77 and newborn babies (0-1 year old) (n = 49) previously scheduled for an unrelated surgical procedure. DNA damage correlated strongly with age in both males (p = 0.029; r = 0.490) and females (p = 0.003; r = 0.600) whereas lipid oxidation (MDA) levels increased with age in males (p = 0.004; r = 0.623) but not females (p = 0.3734; r = 0.200). PARP activity significantly increased with age in males (p<0.0001; r = 0.768) and inversely correlated with tissue NAD(+) levels (p = 0.0003; r = -0.639). These associations were less evident in females. A strong negative correlation was observed between NAD(+) levels and age in both males (p = 0.001; r = -0.706) and females (p = 0.01; r = -0.537). SIRT1 activity also negatively correlated with age in males (p = 0.007; r = -0.612) but not in females. Strong positive correlations were also observed between lipid peroxidation and DNA damage (p<0.0001; r = 0.4962), and PARP activity and NAD(+) levels (p = 0.0213; r = 0.5241) in post pubescent males. This study provides quantitative evidence in support of the hypothesis that hyperactivation of PARP due to an accumulation of oxidative damage to DNA during aging may be responsible for increased NAD(+) catabolism in human tissue. The resulting NAD(+) depletion may play a major role in the aging process, by limiting energy production, DNA repair and genomic signalling.

Midline intravaginal slingplasty for treatment of urinary stress incontinence: results of an independent audit up to 2 years after surgery.

Recently, the midline intravaginal slingplasty (anterior IVS) directed at reinforcing the pubourethral ligament was introduced for treatment of urinary stress incontinence. An independent telephone interview to evaluate urinary symptoms and surgery-related changes in quality of life was performed between 12 and 32 months after surgery. Of 52 women initially enrolled, 3 were lost during follow-up. None of the patients experienced infection, rejection or erosion of the tape. The procedure failed in 7 patients whereas in 42 patients cure of stress incontinence was achieved. This was not only verified by clinical examination at initial follow-up but also confirmed by the patients at the time of the interview. Although about two-thirds of the patients reported urge incontinence and/or voiding difficulties during their interview, the validation of the surgery was rather high and only in a minority did urinary complaints translate into reduced quality of life.