COVID-19 lockdown and the rate of central precocious puberty.

PURPOSE: The aim of our study was to compare the incidence of idiopathic central precocious puberty (CPP) in our highly specialized Endocrinological Center before and after the onset of COVID-19 lockdown; we also aimed to identify any potential difference between girls with CPP from the two different time periods. METHODS: We retrospectively analyzed the auxological profile of 49 girls with idiopathic CPP: 30 with pre-lockdown onset and 19 with post-lockdown onset of the disease. We collected patients' characteristics (medical history, physical examination, baseline and dynamic hormonal assessment, bone age, pelvic ultrasound) and compared them between the two groups. RESULTS: We registered an almost threefold increase in CPP incidence in the 2020-2021 period compared to the previous six years. In post-lockdown patients we found a trend for an earlier diagnosis in terms of both chronological age (p 0.0866) and days between the onset of first pubertal signs and diagnosis (p 0.0618). We also found that post-lockdown patients had a significantly lower hypothalamus-pituitary-gonadal axis activation (lower ∆LH% after GnRH test, p 0.0497), a significantly lower increase in bone age calculated at RUS with TW3 method (p 0.0438) and a significantly reduced ovarian activation in females (lower delta-4-androstenedione levels, p 0.0115). Interestingly, post-lockdown patients were born from mothers with an older age at menarche (p 0.0039). CONCLUSIONS: Besides confirming a significant increase in new diagnoses of CPP in the post-lockdown period, our findings among Post-lockdown girls also suggest a less progressive form of CPP and a stronger environmental influence compared to genetic background in determining the timing of pubertal onset.

ACROMORFO study: gait analysis in a cohort of acromegalic patients.

PURPOSE: In acromegaly, skeletal complications resulted to be associated with low quality of life (QoL) and high risk of falls. The aim of the present study was to perform a quantitative assessment of movement through gait analysis technique in patients with acromegaly. STUDY POPULATION: Thirty-three acromegalic patients [9 with active disease (AD), 14 with controlled disease (CD) and 10 with disease remission (RD)] and 20 healthy subjects were enrolled for the study. MEASUREMENTS: Kinetic and kinematic data were collected with 3D-gait analysis. Kinematic data were processed to compute the Gait Profile Score (GPS), a parameter that summarizes the overall deviation of kinematic gait data relative to unaffected population. RESULTS: The acromegalic group showed longer stance phase duration (p < 0.0001) compared to controls. The GPS and several gait variable scores resulted to be statistically higher in the acromegalic group compared to healthy controls. GPS values were significantly higher in AD compared to CD (p < 0.05) and RD groups (p = 0.001). The AD group presented significantly higher values in terms of hip rotation and ankle dorsiflexion compared to CD and RD groups and with regard to the foot progression compared to RD. Interestingly, patients with RD exhibited a more physiological gait pattern. CONCLUSION: Acromegalic patients showed quantitative alterations of gait pattern, suggesting instability and increased risk of falls. Arthropathy, along with its associated abnormal joint loading, proprioceptive impairment and hyperkyphosis could be contributing factors. Disease control and remission appear to improve postural balance. A better knowledge on walking performance in acromegaly would help to develop specific rehabilitation programmes to reduce falls' risk and improve QoL.

Arthropathy in acromegaly: a questionnaire-based estimation of motor disability and its relation with quality of life and work productivity.

PURPOSE: Arthropathy is a common and disabling complication of acromegaly. Since in this condition radiological findings rarely correspond to functional impairment, we elected to quantify in a large cohort of acromegalic patients: the degree of motor disability compared with data from general population, the impact of joint involvement on quality of life and work productivity, and to look for associated factors. METHODS: In 211 acromegalic patients, 131 with controlled disease and 80 with active disease, eight validated scales were used to evaluate the (i) prevalence and distribution of arthropathy, (ii) degree of motor disability and joint symptoms (VAS, AIMS symptoms and WOMAC), (iii) quality of life (AcroQoL and PASQ) and work capability (WPAI:GH) as consequences of joint complications. RESULTS: Using the WOMAC questionnaire, for which population based normative values are available, a significantly higher prevalence and severity of motor disability was detected in acromegalics compared to the general population from literature. The results provided by the different questionnaires turned out to be highly concordant. All measures of motor disability correlated both with impaired quality of life and motor disability and were worse in females and in patients with higher BMI. CONCLUSIONS: The questionnaires VAS, AIMS symptoms, and WOMAC (this latter both as a whole and with its functionality subscale), with their scores, proved to be the most adequate tools to evaluate motor disability and its consequences on both quality of life and work productivity in acromegaly. Female gender and higher BMI are associated with worse articular symptoms.

A balanced reciprocal translocation t(10;15)(q22.3;q26.1) interrupting ACAN gene in a family with proportionate short stature.

PURPOSE: Few examples of the involvement of a single gene in idiopathic short stature have been described until now. Our aim was to identify the causative gene of proportionate short stature in a large family showing co-segregation of the phenotype with the reciprocal translocation t(10;15)(q22;q24). METHODS: FISH mapping was carried out with BACs and long-range PCR probes to identify the smallest genomic regions harboring the translocation breakpoints. Real-Time RT-PCR was performed in blood after pre-amplification of target genes cDNA. RESULT: The affected family members presented with a final height of between - 2.41 and - 4.18 SDS and very mild skeletal dysmorphisms. Growth rates of the proband and of her cousin, whose childhood and pre-pubertal bone age corresponded to the chronological age, showed a poor growth spurt during treatment with rhGH. However, their adult height was greater than that of their untreated mothers, suggesting efficacy of GH therapy. Breakpoint mapping revealed that the translocation t(10;15)(q22.3;q26.1) disrupts, on 15q, the ACAN gene at intron 1, decreasing its transcriptional expression. CONCLUSIONS: This is the first description of a chromosome rearrangement disrupting ACAN and leading to its haploinsufficiency. ACAN loss of function should be considered a potential underpinning of short patients who display a poor growth spurt and belong to families with autosomal dominant segregation of proportionate short stature. Besides this core phenotype, literature review suggests that advanced bone age, early onset osteochondritis dissecans, osteoarthritis, intervertebral disc disease as well as craniofacial dysmorphisms can be important suggestive phenotypes in affected families.

Decreased adrenergic tone in acromegaly: evidence from direct recording of muscle sympathetic nerve activity.

OBJECTIVE: Sympathovagal imbalance has been shown in acromegaly by indirect measurements of adrenergic tone. Data regarding direct measurement of sympathetic activity are lacking as yet. Aim of this study was to assess the adrenergic tone through direct recording of muscle sympathetic nerve activity (MSNA) in acromegalic patients. DESIGN: Fifteen patients (age 26-66 years, eight women) with newly diagnosed active acromegaly without hyperprolactinaemia, pituitary hormone deficiencies, obstructive sleep apnoea and cardiac hypertrophy, and 15 healthy subjects matched for age, sex and body mass index were recruited. After evaluating anthropometric and echocardiographic parameters, anterior pituitary function, glucose and lipid metabolism, and measuring plasma leptin, direct recording of sympathetic outflow via the microneurographic technique was performed. RESULTS: For similar anthropometric and metabolic parameters in patients and controls, HOMA index was significantly increased in the former (4·2 ± 2·39 vs 1·6 ± 0·19, P < 0·001). Surprisingly, this finding of insulin resistance was accompanied by a marked sympathetic inhibition (MSNA 18·3 ± 8·10 vs 37·3 ± 6·48 bursts/min, P < 0·0001, respectively in patients and controls). A reduction in plasma leptin (1·6 ± 1·04 vs 6·5 ± 2·01 µg/l, P < 0·0001) was also recorded in the patients. MSNA was positively correlated with leptin (P < 0·0001). CONCLUSIONS: Newly diagnosed acromegalic patients without cardiac hypertrophy display a decreased sympathetic outflow in spite of insulin resistance. This finding might be related to hypoleptinaemia.

Assessment of biochemical control of acromegaly during treatment with somatostatin analogues by oral glucose load and insulin-like growth factor I.

BACKGROUND: The use of oral glucose tolerance test (OGTT) in evaluating biochemical control in acromegalic patients on somatostatin analogues (SSA) has recently been questioned. AIM: To gain further insights into this topic, we analyzed basal and nadir GH levels during OGTT in acromegalic patients on SSA. SUBJECTS AND METHODS: Basal IGF-I and GH values, as well as GH levels along the test, were analyzed in 115 standard OGTT performed in 33 acromegalic patients followed up between 1993 and 2009. All patients were on SSA at the time of the study; 22 of them had previously undergone unsuccessful surgery. No patient had undergone radiotherapy. GH suppression was considered normal when the hormonal value fell to <1 µg/l during OGTT. Diagnostic accuracy was analyzed by receiver operating characteristic (ROC) curves. RESULTS: ROC analysis showed that the GH basal value yielding the best specificity (100%) was 3.9 µg/l. All patients with basal GH>3.9 µg/l displayed lack of GH suppression after OGTT and 80% also displayed high IGF-I. Conversely, patients with basal GH<3.9 µg/l presented a variable biochemical pattern with half of them failing to suppress GH after OGTT and 36.6% displaying high IGF-I levels. CONCLUSIONS: Our results show that baseline GH levels >3.9 µg/l are predictive of absent OGTT-dependent GH suppression; however, 20% of these patients display partial biochemical control (normal IGF-I levels). On the other hand, basal GH values <3.9 µg/l are not predictive of GH suppressibility by glucose and are often discordant with IGF-I levels.

Developmental dysplasia of the hip: open reduction as a risk factor for substantial osteonecrosis.

BACKGROUND: Kalamchi and MacEwen (K&M) described a four-group scheme for classifying osteonecrosis (ON) following treatment for developmental dysplasia of the hip (DDH). However, the four groups can overlap in radiographic appearance, making assessment difficult. QUESTIONS/PURPOSES: We (1) describe a simplified K&M classification; (2) determined whether the simplified classification was reliable; and (3) assessed whether differences in the type of reduction or age at reduction resulted in different degrees of ON. PATIENTS AND METHODS: We retrospectively reviewed 300 patients with DDH treated with either open or closed reduction. We included 101 of these patients (133 involved hips). Intraobserver and interobserver reliability testing of the original and our simplified classification was performed. ON occurred in 64 hips (48%). Of these, 22 had original K&M Group I disease (classified as simplified Group A), and 42 had original K&M Groups II, III, or IV disease (classified as simplified Group B). The mean age of the patients at final followup was 12.4 years (range, 6-26.3 years). RESULTS: The interobserver reliability of the simplified classification was greater than that of the K&M classification (0.51 vs 0.33, respectively). Closed reduction after skin traction resulted in a lower incidence of Group B ON than open reduction, regardless of age at reduction. CONCLUSIONS: We propose a simplified and more reliable classification of ON after DDH. With the new classification we found type of reduction (closed with traction versus open without femoral shortening) but not age influenced the risk of ON. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Incorporating environmental stochasticity within a biological population model.

The birth and death transition rates for a population are modelled as functions of both the population size and the environmental condition. An assortment of important theoretical results and techniques that can be utilized to analyze such a population's behaviour is covered. Consequently, these results and techniques are used to study two examples. Firstly, we study a population with a stable equilibrium state, whose per capita birth and death rates are linearly related to the environmental condition. (The environmental condition in turn is modelled as an Ornstein-Uhlenbeck process.) Secondly, we study a population affected by two interdependent environmental factors.

Somatostatin analogs and gallstones: a retrospective survey on a large series of acromegalic patients.

CONTEXT: Development of gallstones (GS) is reported during the use of somatostatin analogs (SA) that are at present the mainstay for the medical treatment of acromegaly. OBJECTIVE: To review the prevalence and clinical and biochemical correlates of GS in acromegalic patients. DESIGN AND SETTING: Retrospective survey on hospital records in acromegalic patients followed up in the last 20 yr in tertiary referral centers. PATIENTS: Four hundred and fifty-nine patients (272 females). MAIN OUTCOME MEASURES: According to SA use and GS occurrence, patients were divided in 4 groups: 1) treated with SA without GS (SA+GS-), 2) GS developed while on SA (SA+GS+), 3) GS without SA use (SA-GS+), 4) neither GS nor SA (SA-GS-). RESULTS: Patients were unevenly distributed in the 4 groups: 232, 125, 38, 64, respectively, pointing to a prevalence of GS in acromegaly of 8.3% at diagnosis with an additional 35% developing GS during SA. GS occurred after 3 months-18 yr (median 3 yr) of SA treatment, were diagnosed after symptoms in 17.6%, were associated to steatosis, ultrasound biliary dilation, and biochemical cholestasis, in 25.6%, 12.8%, and 4% of patients, respectively. Ursodehoxicolic acid was administered after GS occurrence, causing their dissolution in 39% of patients after 3-48 months (median 12). Cholecystectomy was performed in 16.8%of patients in group 2. At multivariate analysis obesity, dyslipidemia, and SA treatment were independent predictors of GS onset, whereas gender and age were not. CONCLUSIONS: GS are a frequent occurrence in acromegalic patients treated with SA, may occur at any time, but are seldom symptomatic or prompt acute surgery. Obesity and dyslipidemia appear to play a major role in the occurrence of GS in acromegalic patients on SA treatment.

Microbiological impressions of teeth, saliva and dietary fibre can predict caries activity.

OBJECTIVES: Mutans streptococci and Lactobacilli on impressions of teeth and caries tests were used to identify caries prone subjects. METHODS: Twenty-seven dental students were examined for caries initially and after 4 years. At the initial examination plaque index; saliva flow, buffering capacity and lysozyme; sucrose and fibre consumption; Lactobacilli and mutans streptococci in saliva and on alginate impressions were measured. Data was analysed using Kruskal-Wallis, Wilcoxon-Mann-Whitney and Spearman's Rank correlation tests and linear discriminant analysis. RESULTS: The best predictor of caries increment was decay. Nine subjects had no caries or restored teeth with caries (Group A); 9 had restored teeth with no caries but developed an average of 8 new decayed surfaces (Group B); 9 had an average of 4.4 decayed surfaces and developed a further 9.6 (Group C). Group A had fewer filled surfaces than Group B (p=0.02) and Group C (p=0.024) a higher flow rate of stimulated saliva than Group B (p=0.02) and Group C (p=0.012). Microorganisms were cultured from all decayed teeth, 98% that developed decay, 89% filled and 69% sound teeth. Fibre intake, saliva flow and the percentage of teeth or sound teeth with Lactobacilli and mutans streptococci gave a specificity of 89%, a sensitivity of 100% and predicted an increase in decay in all Group B subjects while one subject from Group A was misclassified. When teeth with microorganisms were excluded four subjects were misclassified. CONCLUSIONS: Growth of cariogenic microorganisms on alginate impressions, saliva flow and dietary fibre predicted caries activity in most subjects.

Increased lipid peroxidation in adult GH-deficient patients: effects of short-term GH administration.

OBJECTIVE: Adult GH deficiency (GHD) syndrome is characterized by increased risk of atherosclerosis and hence of cardio- and cerebrovascular mortality. Oxidative stress appears to play an important role in early atherogenesis. Oxidized LDL represents an important predictor of cardiovascular risk and is mainly responsible for oxidative damage of the endothelium. Its concentrations are increased in GHD, but the association between this abnormality and oxidative stress is still unclear, due to the discordant results yielded by the few available studies. DESIGN AND METHODS: In 13 GHD patients, plasma lipid peroxide concentrations were measured before and after a 4-month treatment with recombinant human GH (rhGH) and compared with those of 13 age- and sex-matched controls. In the same subjects, the so-called "lag-time", an index of anti-oxidant activity and thus of plasma oxidative balance, was also measured using a fluorescence kinetics method. RESULTS: Before treatment, peroxide levels were significantly higher in patients than in controls (374.0+/-31.52 vs 268.0+/-8.51 U.C., p<0.01), whereas the lag-time was significantly lower (113.0+/-10.70 vs 168.0+/-7.80 min, p<0.01). RhGH administration to patients resulted both in a significant decrease in lipid peroxide levels (from 374.0+/-31.52 to 336.0+/-33.17 U.C., p<0.01) and a significant prolongation of lag-time (from 113.0+/-10.70 to 144.0+/-15.00 min, p<0.01). After treatment, both parameters were no longer significantly different in patients and controls. Lag-time and peroxide levels at baseline did not show any correlation with IGF-I concentrations in GHD patients. After replacement therapy, however, lag-time was positively (r2= 0.62, p<0.01), and peroxide levels negatively (r2=0.41, p<0.05), correlated with IGF-I levels. CONCLUSIONS: These data support the view that adult GHD syndrome is characterized by an unbalance between pro- and anti-oxidant factors with marked preponderance of the former. This abnormality, likely contributing to the increased atherogenic risk of GHD patients, is corrected by short-term GH administration at a dose able to increase, although not to fully normalize, IGF-I levels.

Dental caries at five and twelve years in a South African Indian community: a longitudinal study.

In 1979, 515 of 767 available Indian children born in Lenasia in 1974 were examined and their dental caries status was described. In 1986, 515 of the original 715 were re-examined in order to determine the pattern of dental caries in the primary and permanent dentitions of the same individuals. In contrast to studies in the literature in which treatment records have been used, both investigations were formal epidemiological field studies using calibrated examiners and WHO (1971) caries diagnostic criteria. A firm association was found between caries in the primary and permanent dentitions (r = 0.34).

Trends in arthropod defensive secretions, an aquatic predator assay.

Twenty-five arthropod defensive chemicals were tested on a potential fish predator to assay basic repellency, interniche effectiveness and mimetic interactions among repellents, and predator tolerance to repellents.The defensive secretions of aquatic arthropods are more effective repellents than those of terrestrial or cryptozoic arthropods. Phenolic compounds are more effective than carbonylic or acidic compounds. Repellency is most effective in compounds of reduced water solubility. Repeated exposure to gradually increasing molar concentrations of benzoic acid resulted in a greater acceptability of this compound to fish predators. It is suggested that Mullerian mimicry systems based on large numbers of species may be susceptible to dilution effects in terms of effectiveness.

The onset of eruption of the permanent dentition amongst South African black children.

One thousand and twenty-four children with a mean age of 6.41 yr were examined to determine the mean ages of eruption for the first permanent molars and the permanent central and lateral incisors. The youngest observed age for the eruption of any permanent tooth amongst girls was 4.50 yr and amongst boys, 4.31 yr. The eruption ages were on the whole later than those reported in most African studies, but were very similar to those found for Kenyan African and American blacks.

Predictive value of conditional centile charts for weight and fundal height in pregnancy in detecting light for gestational age births.

OBJECTIVE: To estimate the predictive value of weight and symphysis fundal height (SFH) in pregnancy to detect light for gestational age (LiGA) births. STUDY DESIGN: New conditional centile charts for longitudinal monitoring of maternal weight and fundal height in pregnancy were developed based on the records of 676 women with singleton pregnancies and no complications. The records of these women and of a further sample of 102 women who had LiGA deliveries were used to assess the sensitivity and specificity of the charts in detecting LiGA during pregnancy. RESULTS: Maternal weight is a poor predictor of LiGA births. Fundal height shows moderate predictive ability. The simple cross-sectional chart for fundal height at the 20th percentile cutoff has sensitivity and specificity of 66% in detecting LiGA births. CONCLUSIONS: Monitoring via a cross-sectional chart of fundal height offers a potentially useful screening method. The results of this study add support to arguments that routine weighing in pregnancy should be abandoned.

Dental caries and social factors in 12-year-old South African children.

Dental caries prevalence (percentage caries-free) and experience (DMFS) were recorded, in 414 12-yr-old Indian and 401 white children living in adjacent urban communities with the same fluoride concentration in the drinking water (0.21-0.33 ppm) using WHO (11) criteria. Details of social factors: education level, family income, home space and occupants and parental occupation were obtained by questionnaire. Dental caries was significantly worse in the Indian children with regard to numbers caries-free (30%--white and 40%--Indian) and DMFS mean (sd) (3.65 (3.98) and 2.66 (3.49) working group, respectively). Social class, white or blue collar, family income and room to person ratio were significantly associated with dental caries in the white children but there were no significant associations in the Indian children. Multiple regression analysis showed race and sex to be significant factors.

Dental caries in South African white children aged 1-5 years.

The dentitions of 499 white preschoolchildren aged 1-5 years from a low fluoride area were examined with mirror and probe. The dmft values ranged from 1.0 +/- 2.0 at 1 year of age to 5.1 +/- 4.5 at 5 years of age while the overall mean for the group was 3.7 +/- 4.1. ""Rampant" caries prevalence varied according to the definition used. It is suggested that for epidemiologic studies rampant caries should be defined as a dmft value of 5 or more and that labial caries should be regarded as a specific entity.

Relationships between fluoride in enamel, DMFT index and fluorosis in high- and low-fluoride areas in South Africa.

The DMFT Index, degree of fluorosis (DEGF), and enamel fluoride concentration (F) were determined in 88 children living in a high- and 79 children living in a low-fluoride area in South Africa. The following interrelationships between these parameters were found: in both areas there was a significant negative correlation between log F and age; in the high-fluoride area there was a significant positive correlation between log F and DEGF; and in the combined data from the two areas there were significant correlations between log F and area, log F and age, and log F and DEGF, and a significant association between DEGF and area. There were no significant correlations between DMFT and log F and between DMFT and DEGF.

Patterns of breast and bottle feeding and their association with dental caries in 1- to 4-year-old South African children. 1. Dental caries prevalence and experience.

In order to study associations between breast and bottle feeding and dental caries a questionnaire on feeding habits was completed by trained interviewers for 1,263 children aged 1 to 4 years from five South African communities. Of these, 73 to 94 per cent had been breast fed for mean periods of 9 to 16 months. The types of infant feeding practised (breast, bottle or mixed) varied little within the groups although each group differed significantly from the others for the preferred feeding practice. Using responses to a dietary interview the children were subdivided into those breast fed for 12 months or longer (n = 546), those who had mixed breast and bottle feeding (n = 527) and those who were bottle fed only (n = 190). Caries prevalence increased with the age of the child, more in bottle fed than other groups. Within all feeding groups caries prevalence was lowest among white children and in social class I. The dmfs and dmft scores showed irregular patterns and were significantly influenced by feeding group and the interaction between race and social class.

PIP: The importance of breast feeding in industrialized societies is increasing. As such, it is important to establish whether or not breast feeding on demand for a prolonged period is associated with nursing caries so that the necessary prevention measures may be implemented in both developing and developed countries. The authors present findings from an investigation of breast and bottle-feeding practices and their relationships to dental caries in infants and pre-school children in the Transvaal. The relationship between feeding groups, age, race, social class, and dental decay was explored. Mothers or child carers of 1263 children aged 1-4 years from 5 South African communities were interviewed. 73-94% of the children had been breast fed for mean periods of 9-16 months. Although types of infant feeding varied little within groups, preferred feeding practice differed significantly between groups. 546 children were breast fed for 12 months or longer, 527 had mixed breast and bottle feeding, and 190 were bottle fed only. The prevalence of caries increased with the age of the child and more among the bottle fed than others. The prevalence of caries was lowest among white children and in social class I within all feeding groups.

Patterns of breast and bottle feeding and their association with dental caries in 1- to 4-year-old South African children. 2. A case control study of children with nursing caries.

In a case control study, 109 children with nursing caries (> or = 2 decayed, missing, or filled labial or palatal surfaces of primary incisor teeth) were matched for age, race, gender, and social class to 109 children without nursing caries from the same study areas. Mean dmfs and dmft scores were statistically higher in the nursing caries group but no statistically significant differences were found for feeding patterns between the groups in relation to the prevalence of nursing caries. In the present study nursing caries was found to be unrelated to the length of type of feeding (breast or bottle).