Different effects of calcitriol and parathyroidectomy on the PTH-calcium curve in dialysis patients with severe hyperparathyroidism.

BACKGROUND: The PTH-calcium sigmoidal curve is shifted to the right, the slope of the curve is steeper, and the set point of calcium is increased in dialysis patients with secondary hyperparathyroidism, compared to patients with low-turnover bone disease. These findings could be related to increased parathyroid cell mass and increased sensitivity of parathyroid cells to serum calcium variations in these patients. Calcitriol therapy has been documented to reduce PTH levels by shifting the curve to the left and downward. The effect of a surgical reduction of parathyroid gland mass on the PTH-calcium curve has not yet been investigated. In this study we compared the effects of calcitriol and subtotal parathyroidectomy (PTH) on the dynamics of PTH secretion in response to acute changes of serum calcium in two groups of dialysis patients with severe hyperparathyroidism. METHODS: Fourteen dialysis patients treated for 6 months with high-dose i.v. calcitriol (1-2 micrograms thrice weekly, and 10 dialysis patients who underwent subtotal PTx were studied. The PTH-calcium relationship obtained by inducing hypo- and hypercalcaemia means of low and high calcium dialysis was evaluated before and 2-6 months after treatment. RESULTS: Both calcitriol and subtotal PTx significantly decreased PTH (respectively from 797 +/- 595 to 380 +/- 244 and from 1036 +/- 250 to 70 +/- 34 pg/ml), as well as maximal PTH response to hypocalcaemia (PTHmax), and maximal PTH suppression during hypercalcaemia ( PTHmin). When the PTH-calcium curves were constructed using PTHmax as 100% to factor for differences in absolute PTH levels and to provide an assessment of individual parathyroid cell function, a shift of the sigmoidal curve to the left and downward, and a significant decrease in the set point of ionized calcium (from 1.31 +/- 0.05 to 1.26 +/- 0.05 and from 1.36 +/- 0.09 to 1.22 +/- 0.07 mmol/l) was documented with both treatments. However, the slope of the PTH-calcium curve increased after subtotal PTx indicating that the sensitivity of the parathyroid cell to serum calcium changes increased with PTx, while on the contrary it decreased with calcitriol. CONCLUSIONS: PTH secretion decreases proportionally more with calcitriol than with surgery for a given decrease in the functional mass of parathyroid cells. The change in the PTH-ICa sigmoidal curve induced by subtotal PTx is due to the removal of a large mass of parathyroid tissue with advanced hyperplasia.

[Clinical applications of color-Doppler: the parathyroid glands]. / Applicazioni cliniche del color-Doppler: le ghiandole paratiroidi.

The high-resolution appearance of enlarged parathyroid glands is well known. Thus, real-time gray-scale US alone fails to provide, in ENT surgery, adequate sensitivity and specificity rates to differentiate between parathyroid glands, hypoechoic thyroid adenomas and other hypoechoic neck masses. Since parathyroid tissue, in both normal and enlarged glands, is hypervascular, color-Doppler US is used as a sort of non-invasive angiography to identify parathyroid glands. The combined use of B-mode and color-Doppler US allows the vascular features of thyroid masses to be satisfactorily demonstrated, with easy differentiation between enlarged parathyroid glands, featuring diffuse internal vascularization, and thyroid adenomas characterized by rounded peripheral vessels and also lymph nodes and cysts exhibiting different vascular patterns. We studied 25 patients with clinical and biochemical signs of hyperparathyroidism (19 primary and 6 secondary) submitted to surgery in the last 20 months. Every patient was scanned with both B-mode and color-Doppler US. At surgery, 19 parathyroid adenomas were found--16 of them correctly identified preoperatively with color-Doppler US and 3 false negatives (retrotracheal glands). Moreover, 1 false positive was observed due to a small Plummer's adenoma misdiagnosed as an intrathyroid parathyroid adenoma: both lesions had the same vascular pattern on US images. Sensitivity was 84.5% and specificity 93.7%. In secondary HPT patients, 23 hyperplastic glands were found at surgery--21 of them correctly identified preoperatively by color-Doppler US, with 2 false negatives. No false positive was found. Sensitivity was 87.5% and specificity 100%. Sensitivity does not differ very much from what reported in literature. Specificity is clearly increased by the use of color-Doppler US. The possible source of error represented by Plummer's adenomas lead us to investigate pulsed Doppler capabilities in differentiating Plummer's adenomas from PT glands, since color-Doppler findings were similar in the two conditions. Peak velocities recorded with both color and pulsed Doppler showed velocity to range 6 to 40 cm/s in parathyroid glands (mean +/- SD: 14.6 +/- 11.7) and 38 to 120 cm/s in thyrotoxic nodules (mean +/- SD: 78.4 +/- 23). The statistical analysis of the results showed a highly significant difference between the two groups of velocities. Peak velocities as recorded in the main, vessels of the parathyroid glands with color and pulsed Doppler were correlated with the activity of the parathyroid glands.(ABSTRACT TRUNCATED AT 400 WORDS)

[Role of beta-carotene in the prevention of genotoxic damage in patients undergoing radiotherapy. Monitoring by the micronucleus test in exfoliative cells of the oral cavity]. / Ruolo del beta-carotene nella prevenzione dei danni genotossici in pazienti sottoposti a radioterapia. Monitoraggio mediante test del micronucleo in cellule esfoliate del cavo orale.

Radiotherapic treatment of patients with carcinoma usually causes genotoxis damage. This has been studied recently using the test of micronuclei in esfoliated cells. This test presents methodologic advantages in compared with the classic citogenetic analysis and as it is carried out on esfolieted cells from the oral cavity it faithfully reflects the genotoxic damage undergone by the cells of the basal layer of the epitelium. The preliminary result obtained so far have confirmed the anticlastogenic activity of beta-carotene in fact, the frequence of micronuclei in esfolieted cells from the oral cavity in patients undergoing radiotherapy or undergoing treatment with beta-carotene is inferior to that of patients undergoing treatment with beta-carotene is inferior to that of patients undergoing radiotherapy without the subministration of carotenoids. Treatment with carotenoids does not influence the therapeutic efficiency of radiotherapy treatment. Therefore, the results seem to confirm that indirect ossidaction processes are involved in the mechanism of the clastogenic action of radiotherapia. The carotenoids seem to be able to contrast validly this undesirable effect without interfering with the desirable therapeutic effect.

[The quantitative study of nucleolar organizers (AgNOR) in the diagnosis of laryngeal dysplasias and in the assessment of the prognosis in invasive carcinoma]. / Studio quantitativo degli organizzatori nucleolari (AgNOR) nella diagnosi delle displasie laringee e nella valutazione della prognosi del carcinoma invasivo.

Nucleolar organiser regions (AgNOR) are chromosomal segments in which ribosomal RNA is codified. These structures can be identified in the nuclei of cells in routine histological sections using a silver staining technique which reveals the proteins associated with transcription RNA. The number of AgNOR identified depends on the state of cell proliferation. The purpose of the present study was to evaluate the distribution of AgNOR in normal laryngeal mucosa, dysplastic and neoplastic, in order to establish a possible correlation with the degree of dysplasia and/or the entity of the malignant lesions. Ten slides each of specimens of laryngeal carcinoma, serious dysplasia and middle dysplasia were prepared with the silver staining technique. A count of the NOR in the basal, parabasal, intermediate and superficial levels was made. Findings show an increase in the average value of NOR proceeding from normal tissue to carcinoma in situ and malignant carcinomas. The number of AgNOR was lower always than that observed in the parabasal level. In the intermediate cell section the number of AgNOR was inferior to that in the parabasal level in normal tissue as well as in middle dysplasia, while it remained high in serious dysplasia and in carcinomas, thus indicating a great deal of biological activity in these cases. This method can be employed in order to better individualize those dysplastic lesions which, because of their tendency towards malignancy, must be kept under observation by means of an extremely accurate follow-up.

Extended supraglottic laryngectomy. Review of 84 cases.

Extended supraglottic laryngectomy is a surgical procedure by which the boundaries of standard supraglottic laryngectomy are extended to include the base of the tongue and/or pyriform sinus and/or one of the arytenoids, according to the extent of epilaryngeal or extralaryngeal invasion by vestibular cancer. We report the results of 84 extended supraglottic laryngectomies performed by our group from 1970 to 1980. Besides the highly favorable 5-year cure rate (75%), full functional rehabilitation followed in all but three patients, who were therefore submitted to secondary total laryngectomy. Rehabilitation time is often somewhat longer than in standard supraglottic laryngectomy, especially when an ample resection of the base of the tongue is required. Combined resection of the base of the tongue, aryepiglottic fold, and one of the arytenoids may further lengthen the rehabilitation period. We believe that extended supraglottic laryngectomy should be performed more often, not only for actual invasion, but also for suspected invasion of extralaryngeal structures.

Functional neck dissection: an evaluation and review of 843 cases.

After briefly reviewing the principles, indications, and merits of functional neck dissection, the results of 1200 neck dissections performed on 843 patients in the period 1961-1979 are presented. They compare very favorably with those reported for classic (radical) neck dissection by other leading authors; however, a retrospective analysis of data derived from material of different origin is hardly possible and has a disputable value. Therefore, we decided to compare our data on functional neck dissections (FND) with those of classic neck dissections (CND) performed by the same surgical team at the same clinic in the period 1948-1960. The clinical material was largely the same in both cases, and the data were collected and analyzed using the same criteria. In both series, neck dissections were divided into elective and curative. It could be demonstrated that the number of neck recurrences observed in the dissected necks is the same for FND and CND in curative dissections, while it is considerably lower for FND in elective neck dissections. This of course does not prove improved radicality in FND, but only proves that a systematic bilateral elective neck dissection in N0 cases affords improved cancerological safety. This radical bilateral approach to regional lymph nodes is made possible routinely by FND which avoids the problems of unnecessary mutilation. The figures produced speak in favor of a wider adoption of FND especially for expanding the indications to elective treatment of regional lymph nodes in cancer of the head and neck. Elective neck dissection is made practically harmless by this newer technique and averts the dreadful appearance of late metastases in N0 cases.

Reconstruction of the hypopharynx following extensive loss of mucosa.

Mucosal loss of the hypopharynx, following pharyngostome or wide resection of carcinoma, poses problems for repair. The authors emphasize a reconstructive procedure based on the use of three elements combined together in various ways: residual strip of mucosa of the posterior pharyngeal wall, a musculomucosal pedicled flap obtained from the base of the tongue, a pectoralis major musculocutaneous flap. Thus any defect of the hypopharynx can be repaired in one stage. The safety of the procedure is well tested with good clinical results and lack of complications.

Supraglottic laryngectomy: 30 years of experience.

A review of 467 cases of supraglottic laryngectomy operated during the last 30 years is presented. Cases have been subdivided into groups according to stage and TNM classification. By far the most numerous in this series were T2 cases. No cases prevailed over N+ by 4:1. Stage II cases represented about 60% of the total. Results are analyzed according to TNM and staging. The average overall 5-year cure rate is 75%. The influence of factors other than TNM and staging upon results is also considered. Supraglottic laryngectomy may be extended to include one arytenoid, the base of the tongue, or both, with approximately equal results. Practically all cases had en bloc bilateral functional or classic neck dissection for threatening or actual lymph node metastases. This may have contributed to a higher number of successes. Combined surgery and radiotherapy is occasionally indicated, but rarely improves the prognosis of severe cases. Site and type of recurrences are considered and their treatment and prognosis are discussed. On the basis of the present study the clinical value of supraglottic laryngectomy is further assessed.

Some effects of the stimulus repetition rate on N1 and N2 in transtympanic and surface recordings.

The early auditory evoked electrical activity has been recorded in man at the promontory (transtympanic approach) and on the scalp vertex-mastoid derivation), in response to clicks delivered at different rates. Latency and amplitude of the first two peaks (N1 and N2), as a function of the repetition rate, have been measured and compared. The differences between the latencies of transtympanic and surface N1 are very small, at any rate, with a maximum value of 0.08 msec. In the transtympanic recording, the latency difference between N2 and N1 is constant throughout the whole range of rate values, from 3 to 100 clicks per second. In the surface responses, on the contrary, the latency difference between N2 and N1 tends to increase as the rate is increased. The amplitude of the transtympanic N2 is consistently reduced at click rates above 20-50 per second (more markedly than the amplitude of N1), while the amplitude of the surface N2 is much more insensitive to the rate increase. Some implications of these results are discussed with respect to the origin of N2 in the two recording conditions.

The evolution of the vestibular apparatus according to the age of the infant.

In 56 full-tem A.G.A. infants and in 27 infants of a minimal age of 15 days with a neurological "risk" (full-term small for gestational age, S.G.A.), the nystagmic response to vestibular stimulation (rotatory and torsion swing test) was examined. A delay in the appearance of a response to the labyrinthic stimulus and a persistence of the prevalence of the slow phase of the nystagmus appeared clearly higher in the "risk" infants. The statistical difference of the response between the two groups was highly significant. This allowed us to conclude that the vestibular test appears to the one of the most useful in evaluating the sensorial maturation of S.G.A. infants.

Use of submandibular flap to close pharyngostomes and other defects of lower anterior neck region.

We describe the use of a suprahyoid flap for reconstruction in the lower anterior neck. It has been most useful for immediately closing pharyngostomes and for resurfacing defects from the excision of squamous cell carcinoma of the larynx or other neoplasms involving the skin. This flap provides a good deal of viable tissue, it can easily be rotated without a delay procedure, and the donor area is closed by direct suture. We present our experience with 22 cases.

Our experience with pharyngoesophageal reconstruction.

Our experience with 11 cases of cervical esophageal reconstruction following excision of the hypopharynx and conservative neck dissection is reported. For the reconstructive procedure, we utilized a full-thickness skin graft from the penis according to Kaplan and Markowicz in 2 cases and a deltopectoral flap according to Bakamjian in 9. Critical evaluation of the clinical follow-up has led us to prefer the second method. It seems, in fact, to be the solution of choice in this kind of surgery, for the deltopectoral flap offers a generous source of viable skin due to its good blood supply.