Evaluation of nephrotoxicity and ototoxicity of aminosidine (paromomycin)-allopurinol combination in dogs with leishmaniosis due to Leishmania infantum: A randomized, blinded, controlled study.

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.

Asymptomatic Achilles, patellar, and quadriceps tendinopathy: a longitudinal clinical and ultrasonographic study in elite fencers.

Lower limb tendon changes detected at imaging are common among asymptomatic athletes. We aimed to prospectively assess the clinical status, tendon structure, and vascularity of lower limb tendons of elite fencers, and predict the risk of developing symptoms over time. Clinical examination, changes at ultrasonography (US), and Power Doppler (PD) flow of both the Achilles, patellar, and quadriceps tendon were assessed in 37 elite fencers in January 2007 and 3 years after. Two hundred and twenty-two tendons were examined. At the last appointment, patellar tendons diagnosed as abnormal at baseline were more likely to develop symptoms than those normal at baseline (P < 0.05, Fisher's exact test), while US and PD abnormalities on Achilles and quadriceps tendons were no predictive for development of symptoms over years. A very low percentage of tendons diagnosed as normal at baseline (1.45%) showed US abnormalities at 3-year follow-up. In asymptomatic elite fencers, structural changes are relatively common at US and PD assessment of Achilles, quadriceps, and patellar tendons. It seems unlikely that additional PD investigations provide further information or change prognosis in patients with US diagnosis of tendinopathy.

Isolated radial tears of the lateral meniscus midbody: a case series of professional athletes treated with outside-in repair.

PURPOSE: The main aim of the study is to assess clinical and functional outcomes of arthroscopic outside-in repair of isolated radial tears of the midbody of lateral meniscus in professional athletes and to evaluate the return to the sport activity after surgery. METHODS: A retrospective data collection on professional athletes with isolated complete lesion of the midbody of lateral meniscus, treated with arthroscopic outside-in repair was carried out. Outcome measures included functional assessment, Limb Symmetry Index (LSI) and Hamstring Quadriceps Ratio (HQR) and Lysholm score collected before surgery and at 4-month follow-up. Data on return to sport practice and re-injury were also retrieved. RESULTS: Fourteen patients satisfied the selection criteria. Full return to professional sport activity (Tegner 10) was registered in the 86% of the cohort at 4 months after the surgery. Functional testing of the athletes showed a return of the LSI and HQR to the pre-surgical condition, demonstrating a full recovery of the functional ability and muscle strength. Similarly, clinical evaluation through Lysholm score showed an improvement, reaching an average of 97.7 points at 4 months follow-up. CONCLUSION: A good functional recovery and a high rate of return to play has been observed in a population of professional athletes, at 4 months after outside-in repair.

Achilles tendinopathy in club runners.

Ultrasound (US) changes within the Achilles tendon are present in asymptomatic Achilles individuals. We assessed the association of US signs with symptoms of Achilles tendinopathy in a study group of club level running athletes and in a control group of athletes training at least 2 times per week. The Achilles tendon was assessed in its entirety on longitudinal US scans, at the musculotendinous junction (MTJ), the calcaneal insertion site, and at a midtendon point. 25 middle distance runners, 19 males and 6 females, aged from 18 to 58, were enrolled in each group. When compared to control athletes, club level runners presented significantly increased tendon thickness (p=0.046) at the musculo-tendinous junction, and increased tendon thickness, with no statistical significance, at the other landmarks points. Although club level runners were significantly more symptomatic and predisposed to develop signs of tendinopathy than control athletes (p=<0.001), ultrasound abnormalities were not significantly associated with local symptoms complained at the US investigation time. Prospective studies on asymptomatic athletes are needed to define the predictive value of US signs of Achilles tendinopathy in the development of symptoms in the long-term.

Canonical and uncanonical pathogenic germline variants in colorectal cancer patients by next-generation sequencing in a European referral center.

BACKGROUND: Despite increasing use of next-generation sequencing (NGS), data concerning the gain in germline pathogenic variants (PVs) remain scanty, especially with respect to uncanonical ones. We aimed to verify the impact of different cancer predisposition genes (CPGs) on colorectal cancer (CRC) in patients referred for genetic evaluation. MATERIALS AND METHODS: We enrolled for NGS, by Illumina TruSight Cancer panel comprising 94 CPGs, 190 consecutive subjects referred for microsatellite instability (MSI) CRC, polyposis, and/or family history. RESULTS: Overall, 51 (26.8%) subjects carried 64 PVs; PVs coexisted in 4 (7.8%) carriers. PVs in mismatch repair (MMR) genes accounted for one-third of variant burden (31.3%). Four Lynch syndrome patients (20%) harbored additional PVs (HOXB13, CHEK2, BRCA1, NF1 plus BRIP1); such multiple PVs occurred only in subjects with PVs in mismatch syndrome genes (4/20 versus 0/31; P = 0.02). Five of 22 (22.7%) patients with MSI cancers but wild-type MMR genes harbored PVs in unconventional genes (FANCL, FANCA, ATM, PTCH1, BAP1). In 10/63 patients (15.9%) with microsatellite stable CRC, 6 had MUTYH PVs (2 being homozygous) and 4 exhibited uncanonical PVs (BRCA2, BRIP1, MC1R, ATM). In polyposis, we detected PVs in 13 (25.5%) cases: 5 (9.8%) in APC, 6 (11.8%) with biallelic PVs in MUTYH, and 2 (3.9%) in uncanonical genes (FANCM, XPC). In subjects tested for family history only, we detected two carriers (18.2%) with PVs (ATM, MUTYH). CONCLUSION: Uncanonical variants may account for up to one-third of PVs, underlining the urgent need of consensus on clinical advice for incidental findings in cancer-predisposing genes not related to patient phenotype.

New solid state laser system for SPES: Selective Production of Exotic Species project at Laboratori Nazionali di Legnaro.

The Selective Production of Exotic Species project is under construction at Laboratori Nazionali di Legnaro-INFN. The aim of the collaboration is to produce highly pure Radioactive Ion Beams (RIBs) from fission fragments of a uranium carbide (UCx) target activated by a cyclotron proton beam. In order to select a specific atomic species, the main tool to be applied is the resonant laser ionization technique. We have just completed the installation of a dedicated all solid state laser system whose elements are tunable to transitions of all the elements/isotopes of interest for the project. The new laser system is based on three Titanium:sapphire laser sources, independently pumped by three Nd:YLF pump lasers, and it can be coupled to two high harmonic generation (second harmonic generation, third harmonic generation, and fourth harmonic generation) setups. The power, wavelength, and position of the laser beams are continuously monitored and stabilized by using automated active systems to improve the beam production stability of RIBs. This paper presents the main features of the laser system and examples of application of a laser ion source, including a first demonstration of photoionization of stable silver, one of the most requested elements for RIB application.

Platelet rich plasma and tendinopathy: state of the art.

Platelet-rich plasma (PRP) is increasingly used in the management of tendon injury in sports, supposedly accelerating the process of healing, tissue regeneration, and return to play. However, the scientific clinical evidence to support its use is scanty, and more level I studies need to be performed to justify its widespread use.

Tendinopathy and inflammation: some truths.

Overuse tendinopathies are a common cause of pain and disability in athletes. According to histological findings, it is a failed healing response to overuse tendon injury. In obesity, macrophages and mast cells migrate to adipose tissue, and the resulting decreased availability of immune circulating cells should be responsible for less effective immune responses to acute tendon injury. In diabetic patients, free glucose molecules attach to collagen, alter collagen solubility, increase resistance to enzymatic degradation, and impair cross linking, contributing to the subsequent development of chronic tendinopathy secondary to a failed healing response to a tendon insult. Prolonged systemic, low-grade inflammation and impaired insulin sensitivity act as a risk factor for a failed healing response after an acute tendon insult, and predispose to the development of chronic overuse tendinopathies. Further studies may reveal novel therapeutic treatment approaches.

[Italian consensus on the recommendations about the use of methotrexate for the treatment of rheumatic diseases with a focus on rheumatoid arthritis: results from the "3E initiative"]. / Consensus italiana sulle raccomandazioni per l'utilizzo del methotrexate nelle malattie reumatiche con focus sull'artrite reumatoide: i risultati della "3E initiative".

OBJECTIVE: To develop a set of national evidence-based recommendations for the use of Methotrexate (MTX) in daily clinical practice. METHODS: A panel of 37 Italian Rheumatologists reviewed 10 international recommendations formulated during the "3E (Evidence, Expertise, Exchange) initiative" for the year 2007-8, following a systematic literature search in Medline, Embase, Cochrane Library, and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts and the revision of selected papers and the appraisal of Oxford levels of evidence. Moreover, the same panel by the same methodology formulated further 5 recommendations on topics previously selected by Italian representatives to 3E initiative. The agreement about the set of proposed recommendations was stated by a consensus process and the potential impact on clinical practice was assessed. RESULTS: International Recommendations were analysed and changed when appropriate. In addition, 5 national recommendations were developed by identifying 6371 references, selecting and evaluating the 29 ones satisfying Evidence Based Medicine principles. CONCLUSIONS: A set of 15 national recommendations for the use of MTX in daily clinical practice was developed. These recommendations are evidence-based and integrate the expertise of a large panel of Italian rheumatologists.

Placebo-controlled pilot study of the effects of an eggshell membrane-based supplement on mobility and serum biomarkers in dogs with osteoarthritis.

Osteoarthritis (OA) is a debilitating disease in dogs. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat OA; however, many dogs do not obtain adequate pain relief with an NSAID alone. This pilot study evaluated the systemic anti-inflammatory and mobility enhancing effects of an eggshell membrane-based nutritional supplement in dogs with OA-associated pain and mobility impairment. Twenty-seven dogs with OA-associated pain were enrolled into a randomized, double-masked, placebo-controlled, proof of principle pilot study and received either placebo or an eggshell membrane-based nutritional supplement over a 12-week period. Inflammatory biomarkers (IL-2, IL-6, IL-8, tumor necrosis factor-α, C-reactive protein, S100A12, and N-methylhistamine) were measured at Day 0 and Day 84. Owner questionnaires (CBPI and LOAD) were completed at Day 0, Day 42, and Day 84. Differences between groups over time were calculated. Twenty-two dogs completed the pilot study. Inflammatory biomarker IL-2 decreased in the supplement group, compared to the placebo group. Although small, the difference was statistically significant at an alpha of 0.1 (P=0.069). LOAD scores were numerically lower in the supplement group, but not significantly different from the placebo group at Day 0. Day 84 LOAD scores were significantly lower in the supplement group compared to the placebo group (P=0.034). CBPI results did not show the same pattern. The changes in biomarkers and LOAD scores were small, and do not provide definitive evidence of positive effects. However, these pilot results provide a rationale for performing a larger placebo-controlled study of the potential effects of the eggshell membrane-based nutritional supplement.

Development, analytical validation, and initial clinical evaluation of a radioimmunoassay for the measurement of soluble CD25 concentrations in canine serum.

During immune activation, CD25 is expressed by T cells, and its soluble form (sCD25) is released into the extracellular matrix and the bloodstream. In humans, serum sCD25 concentrations are used as a surrogate marker for autoimmune diseases, malignancies, and transplant rejection. However, a canine-specific assay for the measurement of sCD25 in dog serum has not previously been described. Therefore, the aims of this study were to develop and analytically validate a radioimmunoassay to measure sCD25 in canine serum, to establish a reference interval for canine sCD25, and to test the clinical utility of this assay with serum samples for dogs with various diseases. A competitive radioimmunoassay (RIA) was developed and analytically validated. Analytical validation consisted of lower limit of detection (LLOD), dilutional parallelism, spiking recovery, and intra- and inter-assay variability using pooled surplus canine serum samples. A reference interval was established in healthy dogs and serum samples from dogs with various types of neoplasia, IBD, liver disease, suspected pancreatitis, or suspected small intestinal disease and serum samples with an increased C-reactive protein concentration (CRP) were analyzed to test the clinical utility of the assay. LLOD was calculated to be 0.5 ng/mL. The mean (±SD) observed-to-expected ratio (O/E) for serial dilutions was 101.7 ±â€¯14.0%, and the mean (± SD) O/E for spiking recovery was 93.2 ±â€¯4.2%. Coefficients of variation (CVs) for intra-assay variability were ≤12.5% (mean ±â€¯SD: 7.5 ±â€¯4.2%), and inter-assay CVs were ≤15.7% (mean ±â€¯SD: 11 ±â€¯4.4%). A reference interval (RI) for canine sCD25 of 1.2-4.2 ng/mL was established from a population of 112 clinically healthy dogs. Dogs with neoplasia and dogs with suspected small intestinal disease had decreased concentrations of serum sCD25 when compared to healthy dogs (p < 0.0001, respectively). However, the majority of clinical samples used in this study were within the reference interval. Median concentrations of serum sCD25 were 1.9 ng/mL for healthy dogs. Dogs with cancer, IBD, liver disease, suspected pancreatitis, or suspected small intestinal disease, as well as sera with an increased serum CRP concentration, had median serum sCD25 concentrations of 1.6 ng/mL, 2.1 ng/mL, 2.2 ng/mL, 1.7 ng/mL, 1.5 ng/mL, and 1.8 ng/mL, respectively. Thus, the RIA described here is linear, accurate, precise, and reproducible for measuring sCD25 in canine serum. However, this assay shows little clinical utility of sCD25 as a biomarker for dogs with inflammatory, autoimmune, and/or neoplastic conditions.

Anterior Medial Meniscal Root Tears: A Novel Arthroscopic All Inside Repair.

BACKGROUND: Management of tears of the anterior and posterior roots of the meniscus is still controversial. We wish to propose a simple technique of suture anchor to repair tears of the anterior root of the medial meniscus. METHODS: Twelve patients, active males, underwent arthroscopic repair of the anterior meniscal horn between 2009 and 2011. All were assessed postoperatively at an average follow-up of 1 year after the index operation. RESULTS: At the last appointment, the average Lysholm scores was improved from a pre-operative average value of 48±17 to a postoperative value of 91±7 (P<0.001); five patients (45.3%) were scored as excellent (≥95), and 7 (54.6%) as good (85-94). At the last appointment, 8 of 9 active patients practiced sport at the same preoperative level, 1 (8.5%) had changed to lower level of activity. No technique related complications were evident.

Teriparatide in Fracture Non-Unions.

BACKGROUND: The use of teriparatide in the management of fracture disorders is poorly documented. This study aims to show that teriparatide administration may improve the healing process in patients with nonunions after open fixation of traumatic fractures of the lower limb. METHODS: Four patients received Teriparatide for management of non-unions after open fixation of traumatic fractures of the lower limb. RESULTS: Teriparatide administration resulted in adequate bone callus over the site of nonunion in all the patients, and clinical and radiographic evidence of sound union. CONCLUSIONS: The efficacy of teriparatide in delayed or non unions is still unclear. It may induce an angiogenetic response which counteracts the features responsible for development of non-union. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Tissue preserving total hip arthroplasty using superior capsulotomy.

OBJECTIVE: The goals of a tissue-preserving minimally invasive approach to the hip are to allow early short-term recovery, achieve hip joint stability, minimize muscle strength loss from surgery, spare the peri-articular soft tissues, and allow unrestricted motion in the long term. INDICATIONS: Hip arthroplasty in patients with no pre-existing hardware, with a sufficient space between the acetabular rim and greater trochanter; management of subcapital femoral fractures in older patients. CONTRAINDICATIONS: Protrusio acetabuli. Joint stiffness. This is the main concern when undertaking the superior capsulotomy. Stiffness may result from bone causes, including ankylosis, large osteophytes, bone bridges etc., extra-articular retraction of surrounding soft tissues with capsular contracture of both ligaments and muscles, or a combination of bony and soft tissues causes, resulting in limited adduction. Indeed, maximal adduction is necessary to increase the distance between the apex of the greater trochanter and the superior acetabular edge. In the approach described in the present article, the real limitation is the impossibility to introduce a straight stem through the trochanteric fossa without weakening the trochantericarea. If adduction is restricted, excessive lateralization of the femoral stem would result in postoperative pain and discomfort, especially as we advocate immediate full weight bearing. Even though patients fare better when the trochanteric area is intact, many types of stem such as the GTS (Biomet), or stem Microplasty (Biomet) or even stem Parva (Adler Ortho) may pressurize the internal bone of the trochanteric structures. Therefore, these stems may be implanted in maximal hip adduction. This is the case in coxa profunda or coxa vara, which require more invasive and destabilizing surgical approaches. SURGICAL TECHNIQUE: Lateral position, 5-8 cm incision from the tip of the greater trochanter, identification and transaction of piriformis tendon. Anterior mobilization of the gluteus minimus and exposure of the trochanteric fossa. Removal of the superior portion (bone block) of the head and neck, and preparation of the femoral canal. Preparation of the acetabulum. Complete muscle relaxion is helpful to proceed to satisfactory trial reduction. POSTOPERATIVE MANAGEMENT: Patients may progress to motion and weight bearing without restriction. RESULTS: From April 2009 to December 2010, the first author operated on 463 patients, 275 for osteoarthrosis of the hip, and 188 for subcapital fractures of the femoral neck. Thereof, 375 (75 %) patients could walk with full weight within 6 h from the operation, and climb stairs 24 h later with low loss of blood, and rapid recovery.

The management of chronic rupture of the Achilles tendon: minimally invasive peroneus brevis tendon transfer.

We hypothesised that a minimally invasive peroneus brevis tendon transfer would be effective for the management of a chronic rupture of the Achilles tendon. In 17 patients (three women, 14 men) who underwent minimally invasive transfer and tenodesis of the peroneus brevis to the calcaneum, at a mean follow-up of 4.6 years (2 to 7) the modified Achilles tendon total rupture score (ATRS) was recorded and the maximum circumference of the calf of the operated and contralateral limbs was measured. The strength of isometric plantar flexion of the gastrocsoleus complex and of eversion of the ankle were measured bilaterally. Functional outcomes were classified according to the four-point Boyden scale. At the latest review, the mean maximum circumference of the calf of the operated limb was not significantly different from the pre-operative mean value, (41.4 cm, 32 to 50 vs 40.6 cm, 33 to 46; p = 0.45), and not significantly less than that of the contralateral limb (43.1 cm, 35 to 52; p = 0.16). The mean peak torque (244.6 N, 125 to 367) and the strength of eversion of the operated ankle (149.1 N, 65 to 240) were significantly lower (p < 0.01) than those of the contralateral limb (mean peak torque 289, 145 to 419; strength of eversion: 175.2, 71 to 280). The mean ATRS significantly improved from 58 pre-operatively (35 to 68) to 91 (75 to 97; 95% confidence interval 85.3 to 93.2) at the time of final review. Of 13 patients who practised sport at the time of injury, ten still undertook recreational activities. This procedure may be safely performed, is minimally invasive, and allows most patients to return to pre-injury sport and daily activities.

Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function.

It has been demonstrated that healthy centenarians have more favorable anthropometric characteristics and insulin-mediated glucose uptake than aged subjects. The plasma insulin-like-growth factor I (IGF-I) concentration may account for such differences. Three groups of subjects were studied: 1) adults (< 50 yr; n = 30), 2) aged subjects (75-99 yr; n = 30), 3) centenarians (> 100 yr; n = 19). In all subjects, fasting plasma IGF-I, IGF-binding protein-3 (IGFBP-3), leptin, and lipid concentrations were determined; body composition was assessed by bioimpedance analysis; and insulin-mediated glucose up-take was evaluated by euglycemic hyperinsulinemic glucose clamp. IGF-I declined with advancing age, but no differences between aged subjects and centenarians were found. IGFBP-3 showed a trend similar to IGF-I, but lower values were present in centenarians than in aged subjects. Nevertheless, centenarians had a plasma IGF-I/IGFBP-3 molar ratio greater than that in aged subjects. Centenarians had also a whole body glucose disposal (WBGD) greater than that in aged subjects, but similar to that in adults. Mini Mental State Examination (27 +/- 2.1 vs. 18.3 +/- 3.1; P < 0.02) and Instrumental Activities Daily Living (26 +/- 2.6 vs. 8.4 +/- 4.1; P < 0.001) scores were significantly different in aged subjects and centenarians, respectively. In centenarians, the plasma IGF-I/IGFBP-3 molar ratio correlated with the body mass index (r = -0.55; P < 0.009); the amount of body fat (r = -0.62; P < 0.003); fat-free mass (r = 0.56; P < 0.008); fasting plasma leptin (r = -0.63; P < 0.004), triglycerides (r = -0.58; P < 0.01), free fatty acid (r = -0.64; P < 0.005), and low density lipoprotein cholesterol (r = -0.59; P < 0.009) concentrations; Mini Mental State Examination (r = 0.53; P < 0.0.03); and WBGD (r = 0.64; P < 0.005). All correlations were independent of daily fat and carbohydrate intake and WBGD (P < 0.05 for all). No significant correlations between the plasma IGF-I/IGFBP-3 molar ratio and plasma total (r = 0.31; P = NS) and high density lipoprotein cholesterol (r = 0.34; P = NS) concentrations were present. The correlation between the plasma IGF-I/IGFBP-3 molar ratio and WBGD persisted after adjustment for body fat, fasting plasma insulin concentration, daily carbohydrate and fat intake, and daily physical activity (r = 0.55; P < 0.009), but not after further adjustment for plasma free fatty acid concentration (r = 0.30; P = 0.17). In conclusion, healthy centenarians have plasma IGF-I/IGFBP-3 molar ratio greater than aged subjects. A more elevated plasma IGF-I/IGFBP-3 molar ratio might improve insulin action and plasma lipid concentration in centenarians.

Parity as a thyroid size-determining factor in areas with moderate iodine deficiency.

Among the factors that may influence thyroid size, pregnancy and its goitrogenic effect have been widely investigated, but thyroid volume and pregnancy have never been compared retrospectively, and there are no data on the possible relationship between thyroid size and parity. The purpose of this work was to evaluate the effects of pregnancy on thyroid volume in a moderate iodine deficiency area, to assess the possibility of a relationship between thyroid size and parity status in healthy females. A group of 208 nongoitrous healthy women underwent thyroid volume estimation by ultrasound examination. All subjects were euthyroid and negative for thyroid autoantibodies. They were assigned to different groups, according to the number of completed pregnancies. Five groups were formed (0, 1, 2, 3, 4 or more term pregnancies). Mean thyroid volume increased progressively among the groups: group 0 (14.8 +/- 0.7 mL); group I (16.0 +/- 0.9 mL); group II (17.1 +/- 0.6 mL); group III (18.2 +/- 0.6 mL); group IV (20.3 +/- 0.9 mL). The increment in thyroid volume was statistically significant between group 0 and groups III (P: < 0.01) and IV (P: < 0.001), and also between group I and group IV (P: < 0. 05). No independent effect of body weight and age on thyroid volume was seen. Our results indicate that, in an area with moderate iodine deficiency, the goitrogenic effect of pregnancy is not fully reversible. Moreover, the statistically significant increase in thyroid volume, observed in relation to parity, is the first clinical demonstration of a cumulative goitrogenic effect of successive pregnancies, providing a strong argument to increase the iodine supply during pregnancy, even in conditions with moderate iodine deficiency.

Postintervention serum TSH levels may be useful to differentiate patients who should undergo levothyroxine suppressive therapy after thyroid surgery for multinodular goiter in a region with moderate iodine deficiency.

Recent studies have raised doubts about the efficacy of the postoperative use of levothyroxine (LT4) suppressive doses in patients who underwent thyroid surgery for multinodular goiter. The purpose of this retrospective study was to examine the efficacy of different doses of LT4 in preventing postsurgical recurrences of simple multinodular goiter and to identify a marker that could be useful in discriminating patients with a higher risk of developing recurrence. Two hundred thirty-two patients (57 male, 175 female) operated for nontoxic multinodular goiter were divided into two groups: (I) patients with normal postsurgery thyrotropin (TSH) levels (0.25 to 4.5 mU/L) and (II) patients with elevated postsurgery TSH levels (>4.5 mU/L). All patients were subjected to replacement (1.3 microg LT4/kg/day) or suppressive (1.7 microg LT4/kg/day) doses of LT4, and they were followed for a median period of 6 years (range 2 to 12). No statistical difference was found for sex, age, and postsurgery serum TSH between patients submitted to suppressive and replacement therapy. The ultrasound (US) detection of new postsurgery nodules of at least 0.5 cm maximum diameter was considered a recurrence of disease and was found in 10% of the cases studied. Patients with normal postsurgery serum TSH showed a high recurrence rate (30.4%) when submitted to lower daily doses of LT4. In patients with elevated postsurgery serum TSH, the rate of nodular goiter recurrence did not vary with different types of LT4 therapy. In conclusion, our results suggest that the postsurgical serum TSH is useful for prediction of nodular goiter recurrence, as it reflects the amount of residual functioning thyroid tissue in the cervical area. It may also be indicative of patients who might benefit from LT4 suppressive therapy.

Successful outcome of pregnancy in a thyroidectomized-parathyroidectomized young woman affected by severe hypothyroidism.

Severe hypothyroidism was discovered in a young woman in her 29th week of pregnancy. Previously, at the age of 12 years, she had undergone thyroid surgery for Graves' disease that resulted in persistent hypothyroidism and hypoparathyroidism. After surgical excision, the patient started levothyroxine replacement therapy and had regular control of thyroid function with normal findings throughout the years. The dose of levothyroxine had not been adjusted when the pregnancy started, and at the 29th week of gestation the patient had a thyrotropin (TSH) of 72.4 microU/mL. Ultrasound studies were performed in order to monitor fetal development. The fetal parameters analyzed before the adjustment of levothyroxine therapy showed growth retardation of various degrees. All analyzed fetal parameters (biparietal diameter, cranial and abdominal circumference, humerus and femur length) improved during the last 6 weeks of gestation, showing a good correlation with the newly achieved euthyroid state of the mother. The infant was clinically euthyroid at birth and was found normal at all evaluations of the neonatal hypothyroidism screening program (1, 5, 30 days).