[Necrotizing fasciitis: case reports and review of the literature] / Fascite necrotizzante: descrizione di casi clinici e rassegna della letteratura.

Necrotizing fasciitis is a rare, rapidly progressing infection affecting the superficial fascia and the subcutaneous tissue, accompanied by severe systemic toxicity and multiorgan failure. It is caused by aerobic and anaerobic bacteria, occasionally in a synergistic polymicrobial combination (Type I Necrotizing Fasciitis); in other cases group A -haemolitic Streptoccoccus is the organism responsible for the infection (Type II Necrotizing Fasciitis). The infection often originates from small traumatic injuries or operative wounds and rapidly spreads especially in individuals with identifiable risk factors or immunocompromised patients. Sometimes necrotizing fasciitis occurs when no known portal of entry for bacteria is present. The increasing incidence of necrotizing fasciitis observed may reflect a resurgence of highly virulent mutant strains of group A beta-haemolitic Streptococcus. The pathogenesis, clinical features and treatment of the disease have been reviewed in the light of recent literature. We also report clinical data for four patients with necrotizing fasciitis. They show the importance of early diagnosis and rapid, aggressive and radical surgical intervention. High-dose broad-spectrum antibiotic therapy and intensive medical support are also required to avoid a fatal outcome.

Role of peripherally infused angiotensin II on the human hypothalamic-pituitary-adrenal axis.

Although angiotensin II (AII), a potent vasoconstrictor agent, has been reported to stimulate the hypothalamic-pituitary-adrenal (HPA) axis of laboratory animals, its role in the regulation of this axis in humans appears to be controversial. To examine this question, AII (Val5-AII amide) was infused intravenously into 19 male normal volunteers at the doses of 0, 1, 3.3 and 10 ng/kg/min for 30 min. AII had no effect on plasma ACTH, cortisol, corticotrophin-releasing hormone, arginine vasopressin, and atrial natriuretic factor concentrations, nor did it increase systolic or diastolic arterial blood pressure. On the other hand, AII caused a dose-dependent increase of plasma aldosterone concentrations, suggesting that the doses and the mode of AII infusion were effective. Thus, our data show that peripherally infused AII has no detectable effect on the HPA axis function in humans, at doses capable of stimulating plasma aldosterone secretion, its specific target hormone.

Effect of gonadotrophin-releasing hormone analogue (GnRH-A) administration on serum gonadotrophin and steroid levels in patients with polycystic ovarian disease.

A gonadotrophin-releasing hormone (GnRH) analogue, D-Ser[TBU]LRH-EA10, (GnRH-A), at a dose of 200 micrograms was given daily for 2 months to 6 women with polycystic ovarian disease (PCO). Prior to therapy the patients presented elevated LH, testosterone (T), oestrone (E1) and dihydrotestosterone (DHT) in the circulation. In response to GnRH-A, these subjects exhibited a marked decrease in circulating T, DHT and androstenedione (A) levels as measured 24 h after GnRH-A injection, by 4 weeks and onwards (P less than 0.05). After 2 weeks of daily administration, the serum LH profile, evaluated by sampling at 2, 4, 7 and 24 h after injection of GnRH-A, was not different from baseline, whereas after 4, 6 and 8 weeks the levels were significantly lower (*P less than 0.01). The profile of serum T levels was unmodified at the second week, but significantly decreased thereafter (*P less than 0.01). At the end of treatment, the E1 concentrations, elevated in pre-injection condition, were markedly decreased. These data demonstrate that in PCO subjects, GnRH-A significantly lowered the elevated levels of androgens commonly found in these patients. The close correlation observed between reduced serum LH and androgen concentrations suggests that pituitary desensitization could be responsible for the reduction in androgen levels, and may be evidence for a gonadotrophin dependence of the elevated concentrations of T in these patients.

Kinetics of steroid responsiveness to hCG during chronic inhibition of testicular function by GnRH analogue.

The effect of daily injections of D-Ser-(TBU)6-LRH-EA10 (GnRH analogue (GnRH-A) 100 micrograms sc) on serum testosterone (T), 17 alpha-hydroxyprogesterone (17OHP) and oestradiol-17 beta (E2) was studied in 4 men. During GnRH-A therapy T, 17OHP and E2 were markedly decreased by the end of the second month. Continuous long-term administration of GnRh-A inhibited testicular function. To test whether the biosynthetic pathway was affected by the regimen, a bolus of 2000 U hCG was given to each subject after 10 months of therapy. Evaluation of the kinetics of steroid responsiveness showed a significant release of T in response to the trophic stimulus, with little or no elevation of serum 17OHP and E2. The response seen in these treated men appeared similar to that found in hypogonadotrophic men and prepubertal boys.

hCG-induced maturation of the seminiferous epithelium in hypogonadotropic men.

The effect of long-term hCG administration on sperm output was evaluated in a study in 3 hypogonadal patients with a selective deficiency of gonadotrophins (LH and FSH). The diagnosis of complete hypogonadotropic hypogonadism was based on clinical and hormonal findings as well as testicular histology. Pubertal maturation took place gradually during hCG therapy. 2 out 3 patients, who were azoospermic before treatment, had spermatozoa in their ejaculate after 12 and 24 months of therapy respectively. These effects on spermatogenesis were reversed after hCG withdrawal for 4 months and the patients again became azoospermic. This azoospermia was not reversed by testosterone (T) replacement therapy, or by addition of HMG to T. In vitro, the crude hCG preparation stimulated cAMP accumulation in rat Sertoli cell cultures indicating that this hCG preparation possesses an 'FSH-like' action. The present findings indicate that hCG therapy alone can induce and maintain spermatogenesis in some patients with complete hypogonadotropic hypogonadism.

Down-regulation of prolactin secretion in men during continuous thyrotropin-releasing hormone infusion: evidence for induction of pituitary desensitization by continuous TRH administration.

TRH was administered as a 5-h constant rate iv infusion (5 micrograms/min) to seven healthy adult men. Serum samples were collected at regular intervals for measurement of PRL, TSH, and T3. Serum levels of PRL during TRH infusion increased sharply to maximum level by 40 min, and then, despite continued TRH stimulation, PRL levels declined gradually to a plateau value after 100 min. No further rise in serum PRL was observed when a bolus of 200 micrograms TRH was administered to three subjects after 240 min of infusion. Conversely, an iv bolus of sulpiride (25 mg), a dopaminergic antagonist, given to four subjects after 240 min, brought about a marked increase in serum PRL values above the plateau level. These results are consistent with the interpretation that down-regulation in PRL secretion which follows the initial peak of response most likely represents pituitary desensitization to TRH. During the infusion serum TSH increases in two phases. A first phase of secretion was observed by 40 min followed by a plateau, with a second phase of increase occurring between 80-180 min.

Hydrotestolactone lowers serum oestradiol and PRL levels in normal men: evidence of a role of oestradiol in prl secretion.

The effect on serum PRL levels of lowering serum oestradiol (E2) concentration by short-term administration of an aromatase activity inhibitor, hydrotestolactone (HT), was studied in six healthy male subjects. After HT administration serum E2 levels decreased from 68 +/- 5.8 to 26 +/- 2.5 pmol/l (mean +/- SE, P less than 0.05). These E2 changes were accompanied by a significant decrease in mean 2-h PRL levels from 11.2 +/- 2.1 to 6.5 +/- 1.6 ng/ml mean +/- SE, P less than 0.05). The evaluation of individual percentage change from basal concentrations showed a varying decrease in all subjects. These findings suggest that under physiological conditions E2 may be one of the factors which control blood PRL concentrations in men.

Dynamics of Prl release in galactorrhoeic normoprolactinaemic women.

Prl responsiveness to TRH and sulpiride was evaluated in 14 galactorrhoeic normoprolactinaemic women. Radiological signs of sellar alteration were present in 6 of these patients. Pituitary responses to TRH did not differ from those obtained in a group of 16 healthy women. Serum Prl levels after sulpiride were higher in the patients than in the controls (P less than 0.01). The delta max response was 256 +/- 16 SE vs 158 +/- 10.6 ng/ml in the control group (P less than 0.01). The mean integrated area after sulpiride was also greater 20738 +/- 1263 SE ng/ml/2 h vs 13 188 +/- 408) (P less than 0.01). The markedly enhanced Prl response to sulpiride in our patients with galactorrhoea could be due to a functional disorder of the hypothalamic-pituitary axis or to a lactotrope hyperplasia.

Testicular responsiveness to chronic human chorionic gonadotropin administration in hypogonadotropic hypogonadism.

Steroidogenic responsiveness to long term hCG administration (1500 U three times a week for 23 months) was characterized in 8 males with hypogonadotropic hypogonadism (HH). During hCG treatment, testosterone (T), which was in the prepuberal range under basal conditions, rose considerably to the upper end of the normal range and remained at that level during the 23 months of observation. A 2.5-fold increase was observed in serum levels of 17 beta-estradiol (E2) an increment less than seen with T. The increment in 17 alpha-hydroxyprogesterone was also lower than that in T throughout the study; thus, the 17 alpha-hydroxyprogesterone to T ratio, despite continuous hCG administration, remained low. Serum androstenedione was slightly increased during hCG therapy. No significant changes were observed in serum levels of dehydroepiandrosterone. These data indicate that continuous long term hCG administration stimulated T levels in HH, with a relatively small change in E2. The kinetics of the T and E2 responses to 2000 U hCG, evaluated after 23 months of therapy, indicated that the testicular response was markedly reduced. No increment in T levels was observed at 24 h; the maximal response occurred at 48 h. This pattern of T response supports the idea that partial testicular desensitization occurs in HH patients receiving chronic treatment with hCG.

Dynamic evaluation of prolactin secretion with sulpiride and thyrotrophin releasing hormone in amenorrhoeic and normally menstruating women.

Sulpiride and TRH were used to evaluate the dynamics of prolactin (Prl) release in normoprolactinaemic, amenorrhoeic and normally menstruating women. The two tests were performed in a randomomized order with an interval of 2-3 days. In the normal women the first test was carried out between days 2 and 4 of their cycle. Basal values during the two tests were not statistically different (9.6 +/- 1.2 SE vs. 10.7 +/- 1.4 ng/ml in amenorrhoeic women with sulpiride and 11.3 +/- 1.4 vs. 12.4 +/- 1.7 in amenorrhoeic women during the TRH test). The two tests were performed while the subjects of the two groups had identical serum oestrogen concentrations. The Prl response following TRH administration was similar in both groups (delta max mean 49.5 +/- 12.5 SE and 49.4+/- 8.5 SE in normal and amenorrhoeic women, respectively). In contast, when release by sulpiride administration was studied the normal women had greater Prl release (delta max mean 169.9 +/- 18.2 SE) than amenorrhoeic women (delta max mean 99.8 +/- 9.4). Either the different oestrogen status (lower in amenorrhoeic women than in menstruating women) or the hypothalamic pituitary dysfunction likely to be responsible for the amenorrhoea in our patients, may explain the lower Prl release observed after sulpiride in subjects with amenorrhoea.

Direct evidence in men for a role of endogenous oestrogens on gonadotrophin release.

In six healthy subjects serum oestradiol was selectively decreased by administering an aromatase activity inhibitor, hydrotestolactone (HT). After HT administration serum oestradiol (Oe2) decreased from 18.7 +/- 2.3 (SEM) to 6.7 +/- 0.6 pg/ml whereas testosterone (T) and dihydrotestosterone (DHT) blood levels were not modified. These oestradiol changes were associated with a significant increase in serum LH and FSH concentrations (P less than 0.001). The administration of tamoxifen, an oestrogen antagonist, to 5 subjects caused a sharp increase in LH and FSH levels (P less than 0.001). Oe2 was unchanged after the treatment with tamoxifen, whereas T levels were significantly higher. The sum of these data suggests that oestradiol under physiological conditions plays a specific role in the feedback mechanism of gonadotrophin release.

Some critical considerations on the use of the nomifensine test in the hyperprolactinaemic syndrome.

Nomifensine has recently been proposed as a dynamic test to discriminate tumoral from functional hyperprolactinaemia. In the present study, this test was performed in 9 subjects with radiological signs of sellar alteration and in 6 with no signs of pituitary lesion. Adopting the criterion reported in the previous study, the test was considered positive in 2 subjects of the first group and in 2 subjects of the second group. Therefore, our study indicates that the ability of this test to discriminate subjects with tumorous or non-tumorous hyperprolactinaemia still appears debatable.

Effect of androgens on prolactin (PRL) release in humans.

In order to evaluate whether androgens were able to affect PRL release, testosterone and dihydrotestosterone were injected intramuscularly in male and female subjects. PRL blood levels were not modified by testosterone either in healthy males or in amenorrhoeic women, and PRL release in males proved unaffected by dihydrotestosterone at the dose used.

Effect of cyproterone acetate acutely administered on the pituitary-testicular axis.

The effect of cyproterone acetate (CA) on the pituitary-testicular axis was studied in 6 healthy men. A dose of 300 mg of CA was administered orally in the early morning, after 3 h blood samples were collected using a multiple sample technique. Testosterone (T) levels were decreased by CA in all subjects (p 0.01), LH in all (p less than 0.01) but one whereas 17-hydroxyprogesterone did not show any significant variation. In vitro, using an equilibrium dialysis, CA displaced T from plasma-binding proteins in males at 37 degrees C. The role of testosterone-binding globulin on the effects of CA on the pituitary-testicular axis remains to be clarified.