Changes in TNM stage, reoperation and 131-I ablation rate during the use of newer methods for the preoperative diagnosis of differentiated thyroid carcinoma.

OBJECTIVE: To define and discuss the changes of important risk factors and TNM staging over the last 40 years in patients operated on for differentiated thyroid carcinoma (DTC), resulting from the introduction of newer sensitive diagnostic procedures in the preoperative evaluation of thyroid nodules. PATIENTS: We reviewed the medical records of 1251 patients with postoperative diagnosis of DTC who had undergone initial diagnosis, before surgery, at our unit, between 1971 and 2010. According to the period of diagnosis, the patients were divided into four groups (I, II, III, IV) corresponding to the four decades. RESULTS: The mean age at diagnosis was unchanged over time for both papillary (PTC) and follicular thyroid cancer (FTC). A decrease in the proportion of FTC (group I vs group IV P < 0·01) and a concomitant increase in PTC/FTC ratio was observed particularly in group IV. The significant decrease in the proportion of tumour size of PTC (group I vs group IV, P < 0·01), the increase in the proportion of microcarcinomas, from 22·4% in group I to 53·0% in group IV, P < 0·001, and the decrease in the number of cases with features of aggressiveness have changed the TNM stage towards stages I and II. The overall frequency of patients at high risk was significantly decreased, from 8·0% in group I to 1·8% in group IV. The number of patients who underwent reoperation for the completion of tumour resection and/or radioiodine therapy significantly decreased over time. CONCLUSIONS: The evaluation of thyroid nodules using the newer diagnostic methods was useful in identifying DTC early. Consequently, the reoperation and thyroid remnant ablation rates were reduced.

Urgent thyroidectomy for acute airway obstruction caused by a goiter in a euthyroid pregnant woman.

Pregnancy constitutes a significant factor for thyroid enlargement. However, acute respiratory failure as a result of airway obstruction from an enlarged thyroid gland is an unusual incident. The case presented here concerns a 27-year-old black woman in her 20th gestational week who underwent an urgent operation for removal of a nontoxic, multinodular, mildly substernal goiter that was causing severe upper airway obstruction leading to acute life-threatening respiratory failure. Diagnosis of an extrathoracic tracheal stenosis was based on spirometry with analysis of the flow volume curve and was confirmed by magnetic resonance imaging of the neck. Despite operational risks to the mother as well as the fetus during gestation, an urgent thyroidectomy was carried out successfully. The postoperative period progressed normally and the patient completed her pregnancy with no further respiratory symptoms.

Intracerebroventricular administration of atrial natriuretic peptide prevents increase of plasma ADH, aldosterone and corticosterone levels in restrained conscious dehydrated rabbits.

In order to investigate the effects of centrally administered ANP on plasma ADH, aldosterone and corticosterone levels as well as on blood pressure and on heart rate, 20 male New Zealand White (NZW) rabbits were used. Measurements were made on restrained conscious animals one week after the implantation of an indwelling intracerebroventricular (icv) cannula and two indwelling intravascular catheters (intracarotid and intrajugular). Animals were classified into two main groups, those with water available ad libitum ("euhydrated" group) and those who were dehydrated for 24 h ("dehydrated" group) before blood pressure and heart rate recordings and blood sampling for hormonal determination. Each group's individuals were divided into two subgroups of five animals each. Blood samples were collected at 0 min (control) and 30, 60, 90, 120 min following icv administration of 25 microl of either artificial cerebrospinal fluid (aCSF) (subgroups "aCSF") or human (h) ANP (1 microg) in aCSF (25 microl) (subgroups "hANP"). Blood pressure and heart rate were also recorded at the same times. Plasma ADH, aldosterone and corticosterone concentrations were determined using RIA. The results were analysed by analysis of variance (ANOVA). Blood pressure and heart rate values were unaffected by water deprivation or by ANP administration. Mean plasma corticosterone levels at all times (30-120 min) were significantly higher (p<0.001) than those at 0 min time. Plasma corticosterone levels in the "dehydrated+aCSF" group were significantly higher (p<0.05) than in each of the other groups ("dehydrated+hANP", "euhydrated+aCSF", "euhydrated+hANP"). Plasma corticosterone levels in each of those other groups did not differ significantly from one another. Dehydration resulted in a tendency to increase in aldosterone levels (p<0.07), and icv administration of hANP tended (p<0.08) to prevent in the "dehydrated+hANP" experimental group the increase in aldosterone levels observed in the control "dehydrated+aCSF" group from 30 to 120 min. Dehydration resulted in an increase in ADH levels (p<0.0001), and icv administration of hANP prevented (p<0.05) in "dehydrated+hANP" experimental group the increase in ADH levels observed in the control "dehydrated+aCSF" group from 90 to 120 min. The increase of corticosterone and ADH and the tendency towards increase in aldosterone in the control dehydrated groups could possibly be due to the combined stress stimulus of dehydration and restriction in the restrain box. These results indicate that centrally administered ANP, at the concentration achieved in the present study, neither affects blood pressure and heart rate in conscious restrained euhydrated and 24 h-dehydrated NZW rabbits nor decreases the ADH, aldosterone and corticosterone response to dehydration, but does apparently modulate ADH, aldosterone and corticosterone responses to other stimuli in the dehydrated state. In conclusion, the results of this study confirm that brain ANP may have an inhibitory effect on stimulated ADH, aldosterone and corticosterone release.

Effects of intracerebroventricular administration of atrial natriuretic peptide (ANP) on blood pressure, heart rate and plasma ADH and corticosterone levels in normal and dehydrated rabbits.

In order to investigate the effects of centrally administered Atrial Natriuretic Peptide (ANP) on plasma ADH and corticosterone levels as well as on blood pressure and on heart rate, 20 male New Zealand White (NZW) rabbits were used. Measurements were made on restrained conscious animals one week after the implantation of an indwelling intracerebroventricular (i.c.v.) cannula and two indwelling intravascular catheters (intracarotid and intrajugular). Animals were classified into two main groups, those with water available ad libitum ("euhydrated" group) and those who were dehydrated for 24h ("dehydrated" group) before blood pressure and heart rate recordings and blood sampling for hormonal determination. Each group's individuals were divided into two subgroups of five animals each. Blood samples were collected at 0 min (control) and 30; 60, 90, 120 min following i.c.v. administration of 25 microliters of either artificial cerebrospinal fluid (aCSF) (subgroups "aCSF") or human (h) ANP (1 microgram) in aCSF (25 microliters) (subgroups "hANP"). Blood pressure and heart rate were also recorded at the same times. Plasma ADH and corticosterone concentrations were determined by RIA. The results were analysed by ANOVA. Blood pressure and heart rate values were unaffected by water deprivation or by ANP administration. Mean plasma corticosterone levels at all times (30-120 min) were significantly higher (p < 0.001) than at 0 min time. Plasma corticosterone levels in the "dehydrated + aCSF" group were significantly higher (p < 0.05) than in each of the other groups ("dehydrated + hANP", "euhydrated + aCSF", "euhydrated + hANP"). Plasma corticosterone levels in each of those other groups did not differ significantly from one another. Dehydration resulted in an increase in ADH levels (p < 0.0001) and i.c.v. administration of hANP prevented (p < 0.05) in "dehydrated + hANP" experimental group, the increase in ADH levels observed in the control "dehydrated + aCSF" group from 90 to 120 min. The increase of corticosterone and ADH in the control dehydrated groups could possibly be due to the combined stress stimulus of dehydration and restriction in the restrain box. These results indicate that centrally administered ANP, at the concentration achieved in the present study, neither affects blood pressure and heart rate in conscious restrained euhydrated and 24h-dehydrated NZW rabbits nor decreases the ADH and corticosterone response to dehydration, but does apparently modulate ADH and corticosterone responses to other stimuli in the dehydrated state. In conclusion, the results of this study confirm that brain ANP may have an inhibitory effect on stimulated ADH and corticosterone release.

Bioactive LH in women with polycystic ovaries and the effect of gonadotrophin suppression.

Discrepancies between levels of bioactive LH (B-LH) and immunoreactive LH (I-LH) in polycystic ovarian syndrome (PCO) have been reported previously. Serum levels of I-LH, B-LH (by dispersed Leydig cell assay), FSH, oestradiol (E2) and progesterone (Prog) were measured once to three times weekly over 4 weeks in 13 women with classical clinical, ultrasound and endocrine features of PCO. Eleven women attending for infertility but whose profiles when studied three times weekly by combined endocrine and ultrasound assessment were normal and ovulatory served as controls. Seven of the women with PCO were evaluated during and after 3 weeks suppression with ethinyloestradiol (30 micrograms) plus 150 micrograms either of desogestrel or levonorgestrel; two were given both treatments. Both I-LH and B-LH levels were higher in PCO patients (20 +/- SD 5 U/l and 46 +/- 9 U/l respectively, P less than 0.0001), compared with all phases of the normal cycles except the mid-cycle peak. The B-LH to I-LH (B:I LH) ratio in PCO patients (2.5 +/- 0.7) was higher than in all the control cycle phases (P less than 0.05). I-LH, B-LH, B:I LH ratio, FSH and E2 were all suppressed from the second week of oestrogen-progestogen treatment (P less than 0.01) and returned gradually to pretreatment levels by the third or fourth week after suppression. The LH and FSH levels and B:I LH ratio in PCO patients during suppression were comparable with levels in the early and mid-follicular phases of control cycles but the LH/FSH ratio remained significantly raised (P less than 0.01) at 2.3 +/- 0.7.(ABSTRACT TRUNCATED AT 250 WORDS)

The stability in vitro of bioactive and immunoreactive LH in human blood and plasma.

The degree of stability in vitro of bioactive and immunoreactive LH in human blood, plasma and serum was examined. Bioactivity and immunoreactivity of LH were assayed by the dispersed mouse Leydig cell assay and by standard radioimmunoassay respectively, using the same reference preparation (first international reference preparation for human pituitary LH 68/40 for immunoassay). Bioactive and immunoreactive LH were stable in blood and plasma at 22 degrees C for up to 4 and 24 h respectively, and in blood at 4 degrees C for up to 24 h. There was no loss of biological or immunological LH activity in plasma which had been either snap-frozen and stored at -70 degrees C, allowed to freeze at -20 degrees C and stored at that temperature or kept at 4 degrees C for 24 h and then stored at -70 degrees C. Likewise, the levels of LH in plasma and serum which had been stored at either -20 or -70 degrees C and then thawed and refrozen up to four times remained unchanged. In addition, the biological and immunological activity of LH was not affected after vortexing samples of plasma or serum for up to 60 s. Bioactive LH was also stable in plasma samples after prolonged storage (up to 9 months) at either -70 or -20 degrees C. We conclude that LH bioactivity and immunoreactivity are stable in blood and plasma following a variety of treatments commonly experienced during normal handling of a blood sample after venepuncture.

Trial of 17-hydroxyprogesterone caproate (Proluton Depot) in women with long-standing infertility; failure of estrogen positive feedback the following cycle.

In open and double-blind studies 40 women with long-standing unexplained infertility were investigated and treated with 17 alpha-hydroxyprogesterone caproate (17HPC, Proluton Depot). In the open study, 16 women with a high index of suspicious abortions were given 500 mg 17HPC imtramuscularly (i.m.) weekly for 6-16 weeks. Six of the women received the drug from a time preceding the expected date of a period; 2 of these conceived that cycle and their pregnancies continued to term, while 4 were not pregnant. Ten women (9 with definite previous abortions) were given 17HPC when they suspected (correctly) that they were pregnant. Their pregnancies continued to term in all but 1, who had a premature delivery (still-birth) at 34 weeks. In the double-blind study 24 women were given injections of 17HPC or placebo i.m. at weekly intervals, from about 4 days before the expected period (day -4), provided that the level of progesterone (Prog) (on days -9 to -7) was greater than 10 nmol/l. After placebo no delay in menstruation or disruption of the succeeding cycle was observed. In 14 of 16 cycles in 14 women given 500 mg 17HPC the withdrawal period was delayed by a few days, and then followed by highly erratic bleeding over the next 1-3 months. The dose was therefore reduced to 250 mg 17HPC but the same problem resulted in 8 of 29 cycles in 16 women (including the above studied in later cycles). Regular cycles were eventually restored in all cases but in 3 this necessitated treatment with the contraceptive pill (Microgynon). In most of the post-treatment cycles there was a progressive and prolonged estradiol (E2) rise, which was not preceded by changes either in serum FSH concentration or in the LH/FSH ratio nor associated with the expected positive feedback rise in LH. We conclude that 17HPC disrupts the following cycle, probably by allowing follicular development while interfering with positive LH feedback. None of the patients of the double-blind study had conceived (as evidenced by undetectable hCG levels). Our study confirmed that this progestogen exerts no direct luteolytic effect. However, in order to establish the efficacy or otherwise of 17HPC given before the end of the cycle, women should be selected with a very high index of suspicion of recurrent early implantation failure or abortion.

Postprandial hyperglycemia after ingestion of peeled and non-peeled fruits in type-2 diabetics.

Should diabetics prefer nonpeeled fruits in their diet? To answer this question 27 type-2 diabetics divided into three groups were examined on two different occasions under the same fasting conditions. The first group of patients received 300g of pears with peel and on another day 300g of peeled pears. The second group ate 300g of pears with peel and 230g of peeled pears (the 70g difference represents the weight of the peel). The third group of diabetics consumed 300g of apples with peel and 300g of apples without peel. Blood samples were collected before and 20, 40, 60, 80, 100, 120 and 140 min after fruit ingestion. No significant differences were noted in terms of mean blood glucose, serum insulin and serum triglyceride levels among the two meals (fruits with or without peel). This observation was confirmed in all groups studied. Peeled and nonpeeled fruits appear to produce the same hyperglycemia in type-2 diabetics, in spite of the high fiber content of the peel. Therefore, the suggestion of reducing postprandial hyperglycemia in diabetics by eating nonpeeled fruits does not seem to be justified.

In vitro and in vivo interactions of recent cephalosporins with gentamicin and amikacin.

The in vivo interactions of the aminoglycosides gentamicin and amikacin with the newer cephalosporins cefotaxime, ceftriaxone, ceftazidime and moxalactam were studied in 48 volunteers (28 males, 20 females, median age 54) who consented to participate in the trial. Patients were divided in eight groups according to all possible aminoglycoside/cephalosporin combinations. The in vivo trial was developed in two phases: aminoglycoside alone vs. aminoglycoside/cephalosporin. Each patient served as his own control. The differences in the aminoglycoside blood levels between the two phases were not statistically significant, except at the first post-dose hour in the gentamicin-ceftriaxone combination and at the first and sixth post-dose hours in the amikacin-moxalactam combinations. The in vitro interactions of the same combinations were partly correlated with the in vivo findings.

Ceftriaxone: therapeutic results in various infections and kinetic studies.

Ceftriaxone (Ro 13-9904, Rocephin) was given to 67 patients suffering from 74 various infections. Patients had infections of the urinary tract (36), soft tissue phlegmon (12), infections of the respiratory tract (13), osteomyelitis (7), abscesses (5) and meningitis (1). Infecting organisms were E. coli (26), Proteus spp. (20), P. aeruginosa (7), H. influenzae (6), Enterobacter spp. (6), K. pneumoniae (3), C. freundii (2), S. marcescens (1), S. aureus (4), S. pneumoniae (2), Peptostreptococcus spp. (4) and Clostridium spp. (1). The organisms were often multiresistant. Dosage ranged from 1-2 g once or twice daily i.m. or i.v. The clinical response was excellent in 56 infections (75.6%) while 13 (17.6%) infections were improved and in 5 (6.8%) treatment failed. The pathogen was eradicated in 63 (85.1%), and relapsed in 3 (4.0%) while bacteria persisted in 11 (14.9%). No appreciable side effects or toxicity were observed. Sputum, bile, cerebrospinal fluid and prostatic fluid kinetics revealed ceftriaxone concentrations several times above the minimal bactericidal concentrations required to kill the enterobacteriaceae, but mostly inadequate to inhibit P. aeruginosa strains. Ceftriaxone was a safe and effective drug for the treatment of various infections. However, with the exception of urinary tract infections it should be given with caution in P. aeruginosa infections.