Inequalities in zoster disease burden: a population-based cohort study to identify social determinants using linked data from the U.K. Clinical Practice Research Datalink.

BACKGROUND: Zoster vaccination was introduced in England in 2013, where tackling health inequalities is a statutory requirement. However, specific population groups with higher zoster burden remain largely unidentified. OBJECTIVES: To evaluate health inequalities in zoster disease burden prior to zoster vaccine introduction in England. METHODS: This population-based cohort study used anonymized U.K. primary care data linked to hospitalization and deprivation data. Individuals aged ≥ 65 years without prior zoster history (N = 862 470) were followed from 1 September 2003 to 31 August 2013. Poisson regression was used to obtain adjusted rate ratios (ARRs) for the association of sociodemographic factors (ethnicity, immigration status, individuals' area-level deprivation, care home residence, living arrangements) with first zoster episode. Possible mediation by comorbidities and immunosuppressive medications was also assessed. RESULTS: There were 37 014 first zoster episodes, with an incidence of 8·79 [95% confidence interval (CI) 8·70-8·88] per 1000 person-years at risk. In multivariable analyses, factors associated with higher zoster rates included care home residence (10% higher vs. those not in care homes), being a woman (16% higher vs. men), nonimmigrants (~30% higher than immigrants) and white ethnicity (for example, twice the rate compared with those of black ethnicity). Zoster incidence decreased slightly with increasing deprivation (ARR most vs. least deprived 0·96 (95% CI 0·92-0·99) and among those living alone (ARR 0·96, 95% CI 0·94-0·98). Mediating variables made little difference to the ARR of social factors but were themselves associated with increased zoster burden (ARR varied from 1·11 to 3·84). CONCLUSIONS: The burden of zoster was higher in specific sociodemographic groups. Further study is needed to ascertain whether these individuals are attending for zoster vaccination.

[Mitomycin C after endoscopic endonasal dacryocystorhinostomy]. / Primenenie mitomitsina-S pri éndoskopicheskoi éndonazal'noi dakriotsistorinostomii.

Mitomycin-C (MMC) is the most frequently used agent for prevention of excessive scarring at the osteotomy site after endoscopic endonasal dacryocystorhinostomy (EEDCR), which, however, being applied during the final stage of the surgery, shows questionable effectiveness. AIM: to evaluate the effectiveness of a new administration route of mitomycin C in EEDCR. MATERIAL AND METHODS: The study included 86 patients (95 cases) in the age range of 62.3±9 years with primary acquired nasolacrimal duct obstruction. All patients underwent P.J. Wormald modification of EEDCR and were further divided into 2 groups. In group 1, MMC was injected into the nasal cavity and lacrimal sac mucosa, while in group 2 it was applied locally according to the standard procedure. To measure tissue concentrations of MMC, mucosal biopsies were taken in patients of Group 1. Systemic absorption of MMC was studied through blood samples in both groups. Clinical efficacy was assessed in 14±5 months after surgery. RESULTS: immediately after injection, the average tissue concentration of mitomicyn C in patients of Group 1, was 390±10 µg/g and 30 minutes later - 120±20 µg/g. No mitomycin C was found in Day 1 tissue samples and in any of the blood samples. Positive clinical results were reported in 97.9% of cases from Group 1 and in 87.2% of cases from Group 2. CONCLUSION: The method of injecting MMC during the final stage of EEDCR has proved clinically effective and safe and can be recommended for use in clinical practice.

[Use of optical coherence tomography based lacrimal meniscometry in dacryology]. / Primenenie lakrimal'noi meniskometrii na osnove opticheskoi kogerentnoi tomografii v dakriologii Obzory literatury.

Optical coherence tomography (OCT) based lacrimal meniscometry is currently the most accurate method used to determine dimensions of tear meniscus. According to related literature, the latter gets reliably reduced after treatment of nasolacrimal duct obstructions. However, the relationship between morphometric parameters of tear meniscus and the intensity of epiphora has not been established. Even an adequate study parameter has not been yet identified. AIM: To investigate the significance of OCT based lacrimal meniscometry in determining the extent of insufficiency of lacrimal drainage. MATERIAL AND METHODS: A total of 108 measurements of the lower tear meniscus were taken. Of them, 23 measurements were taken in healthy volunteers, who had no complaints of epiphora, 59 - in patients with epiphora of different intensity, and 26 - in patients after surgical intervention. Meniscometry was performed with RTVue-100-2 (Optovue, USA) optical coherence tomograph. The tear meniscus 'height', 'depth', and coefficient were evaluated. Munk's scores for epiphora were also collected. Spearman's correlation was applied to assess the morphometry results and Munk's scores. A separate analysis was performed for patients who were examined before and after dacryological treatment. Differences were evaluated with the Kruskal-Wallis H test. RESULTS: Statistically reliable differences were found between the meniscus 'height' and 'depth' values at different epiphora intensities (p<0.001 for both parameters; H=25.35 and 22.01, respectively), however, the meniscus coefficients showed no significant difference in these patients (p=0.8, H=1.57). Moreover, there was a highly reliable (p<0.001) medium strength direct correlation between the meniscus 'height' and 'depth' and the Munk's scores (R=0.46 and R=0,48, respectively), while the correlation between the meniscus coefficient and the Munk's scores appeared weak and lowly reliable (p=0.20, R=0.14). CONCLUSION: Lower meniscus morphometry with 'depth' measurement is a comprehensive method to assess the state of lacrimal drainage system. However, it should not be used alone due to significant variations in morphometric parameters, particularly in patients with intensive epiphora.

[Morphological analysis of reparative process at osteotomy site after endoscopic endonasal dacryocystorhinostomy]. / Morfologicheskii analiz protsessovreparatsii v oblasti dakriostomy posle endoskopicheskoi endonazal'noi dakriotsistorinostomii.

Ostium closure due to local reparative processes is the most common cause of recurrence after endoscopic endonasal dacryocystorhinostomy (DCR), but as yet poorly studied. AIM: To perform morphological study of reparative processes at osteotomy site after endoscopic endonasal DCR. MATERIAL AND METHODS: The study included 18 patients (18 women) aged 62.59±10.07 years with nasolacrimal duct obstruction, who underwent endoscopic endonasal DCR (P.J. Wormald modification). Osteotomy site biopsies were taken on days 2, 5, 7, 10, 14, 21, 28, and 60 after the surgery. All the samples were stained with haematoxylin and eosin. For further details on cellular composition of inflammatory infiltrate, 54 samples were also processed into semi-thin sections. The slides were then viewed under Leica DM-2500 (Leica, Germany) photomicroscope. Leica DFC320 digital camera and ImageScope Color software were used for image acquisition and analysis. RESULTS: Morphological examination revealed the predominance of inflammatory cells in biopsy material on day 1 after DCR. On day 14, the number of cells would usually be reduced indicating the completion of the exudative phase of inflammation. Since then, activated fibroblasts prevailed over the rest of cellular elements. Twenty eight days after DCR, proliferating fibroblasts and collagen fibers were present. Sixty days after the surgery, fibrillar component prevailed over cells and showed compaction. CONCLUSION: Our results demonstrate that the reparation process nears completion before day 60 after the surgery. A series of morphological examinations of biopsy material from osteotomy sites has revealed individual features of reparation in nasal and lacrimal sac mucosa after endoscopic endonasal DCR.

[Therapeutic methods of scar prevention at the site of endonasal dacryocystorhinostomy].

Success rate of endonasal dacryocystorhinostomy (DCR) varies from 82% to 91%. The bulk of unsatisfactory results is due to excessive scarring at the site of the created opening (dacryostoma, DS). Mitomycin C is the most extensively studied drug of those affecting regeneration processes, however, the data on its efficacy at DS site is contradictory. Despite ongoing search for new agents able to interfere in the physiological process of scarring, the number of relevant studies is yet insufficient. Thus, development of methods of scarring prevention after endonasal DCR takes the highest priority in dacryology.

[Comparative analysis of the results of balloon dacryoplasty for stenoses at different levels of the vertical portion of lacrimal pathways].

AIM: to compare the effectiveness of balloon dacryoplasty (DCP) for stenoses at different levels of the vertical portion of lacrimal pathways and to establish the necessity of consequent intubation. MATERIAL AND METHODS: A total of 120 clinical cases in 85 patients (66 females and 19 males with the mean age of 53.61 ± 11.82 years) have been analyzed. Patients with cervical stenosis of the lacrimal sac constituted two groups: group 1 (19 patients, 30 balloon DCP surgeries) and group 2 (22 patients, 30 balloon DCP surgeries with Ritleng intubation). Two other groups consisted of patients with nasolacrimal orifice stenosis: group 3 (21 patients, 30 balloon DCP surgeries) and group 4 (23 patients, 30 balloon DCP surgeries with Ritleng intubation). Besides routine examinations, the assessment included collection of Munk's scores for epiphora, evaluation of health-related quality of life, lacrimal meniscometry, lacrimal scintigraphy, contrast enhanced multi-slice spiral computed tomography of lacrimal pathways, and single-photon emission computed tomography. The follow-up period was 6 months. RESULTS: In group 1 a complete recovery was achieved in 18 (60.00%) cases, improvement--in 9 (30.00%) cases, while a relapse occurred in 3 (3.00%) cases; in group 2, there were 18 (60.00%) recoveries, 10 (33.33%) improvements, and 2 (6.67%) relapses; in group 3--12 (40.00%) recoveries, 5 (16.66%) improvements, and 13 (43.34%) relapses; in group 4--19 (63.33%) recoveries, 8 (26.67%) improvements, and 3 (10.00%) relapses. CONCLUSION: Balloon dacryoplasty is effective in restoring patency of occluded lacrimal pathways. Success rate is higher in cervical stenoses of the lacrimal sac than in nasolacrimal orifice stenoses. Ritleng intubation after balloon DCP favors better outcomes in patients with nasolacrimal orifice stenosis.

[Developing the optimal protocol for balloon dacryoplasty].

AIM: To develop the optimal protocol for balloon dacryoplasty (DCP) through an experiment. MATERIAL AND METHODS: The experiment enrolled 12 Chinchilla rabbits (24 eyes). DCP protocol for group 1 (5 rabbits, 10 eyes) implied two dilations of 90 and 60 sec followed by another two of the same duration, while in group 2 (5 rabbits, 10 eyes) all four dilations were of 90 sec. The balloon was moved proximally before the every third dilation. The remaining 2 rabbits (4 eyes) who did not receive balloon DCP constituted the control group. The animals were killed on days 1, 3, 7, and 14. In all cases nasolacrimal duct morphology was studied. RESULTS: By day 14 after the procedure, inflammatory changes in nasolacrimal ducts either had resolved (protocol 1) or persisted (protocol 2).

[Minimally invasive surgery for dacryostenosis: modern trends].

The article presents the results of a monocentric randomized open prospective study conducted from 2008 to 2013. Lacrimal intubation with Mini-Monoka and Monoka silicone stents (mono- or bicanalicular) or with SRS and Ritleng ("FCI", France) stents for dacryostenosis of different localization was performed in 151 patients (203 eyes). The follow-up period was 12 months after the extubation. Patient examination and monitoring included collection of subjective Munk scores for epiphora, lacrimal scintigraphy and bulbar hyperemia evaluation. Though all interventions were proved to be effective, the authors came to the conclusion that, bicanalicular Mini-Monoka and Monoka stents were associated with fewer complications as compared with bicanalicular SRS and Ritleng stents.

Stochasticity and heterogeneity in host-vector models.

Demographic stochasticity and heterogeneity in transmission of infection can affect the dynamics of host-vector disease systems in important ways. We discuss the use of analytic techniques to assess the impact of demographic stochasticity in both well-mixed and heterogeneous settings. Disease invasion probabilities can be calculated using branching process methodology. We review the use of this theory for host-vector infections and examine its use in the face of heterogeneous transmission. Situations in which there is a marked asymmetry in transmission between host and vector are seen to be of particular interest. For endemic infections, stochasticity leads to variation in prevalence about the endemic level. If these fluctuations are large enough, disease extinction can occur via endemic fade-out. We develop moment equations that quantify the impact of stochasticity, providing insight into the likelihood of stochastic extinction. We frame our discussion in terms of the simple Ross malaria model, but discuss extensions to more realistic host-vector models.

Causes of unsatisfactory results of the use of mitomycin-C in endoscopic endonasal dacryocystorhinostomy.

PURPOSE: To study the antifibrotic effectiveness of mitomycin-C in the tissues of the ostium site after it application for endonasal endoscopic dacryocystorhinostomy. MATERIAL AND METHODS: The study included 45 patients (48 cases) with primary obstruction of the nasolacrimal duct. All patients underwent endoscopic endonasal dacryocystorhinostomy (EEDCR). At the final stage of the operation, a swab with MMC was placed in the region of the formed ostium at a concentration of 0.2 mg/ml for 3 min. An ostium was not intubated. After that, biopsies of the mucous of the nasal cavity and lacrimal sac were performed to study the morphological changes that occur in the tissues overtime, as well as to calculate the concentration of the drug in the tissues. RESULTS: According to the chemical analysis, the concentration of MMC immediately after application was 0.626 ± 0.176 µg/g; after 30 min the concentration of the drug was reduced to 0.23 ± 0.06 µg/g; a day after the operation the drug was not found in the tissue samples. Morphological study established that the repair processes occurring in the mucosa of the nasal cavity and the lacrimal sac after EEDCR are similar to the reparative processes without the use of MMC. The effectiveness of surgical treatment: "positive results" - 77.1% of cases, "relapses" - 22.9% of cases. CONCLUSIONS: Application of MMC for prevention of excessive scarring after EEDCR is impractical as it is not possible to achieve antifibrotic concentration of the drug at dacryocystorhinostomy ostium site using this method.

Renal wastage of insulin in children with diabetes mellitus.

In normal human beings the percentage of serum insulin excreted in the urine is constant over a wide range of values. The quantity of immunoreactive insulin found in the urine is believed to reflect the level of free insulin in the serum. Immunoreactive insulin was measured in the urine of nondiabetic children and diabetic children receiving exogenous insulin. Children with diabetes mellitus excreted greater amounts of immunoreactive insulin (18.5+/-8 muU./mg. creatinine) than did nondiabetic children (11.9+/-5 muU./mg. creatinine). This difference was statistically significant (p less than 0.0005). Children with "poor glycemic control" excreted a greater portion of their administered insulin dose than did those with "good control." The renal wastage of insulin correlated (r=0.94) with the duration of insulin treatment but not with the quantity administered. Antibody binding of serum insulin may explain in part these observations, but an acquired defect in the renal tubular reabsorption of insulin may also exist. Modifications in the management of diabetes that reduce the renal wastage of insulin may improve the metabolic stability of children with "poor diabetic control."

Magnetic resonance imaging in patients with hypopituitarism.

In patients with hypopituitarism, magnetic resonance (MR) imaging of the hypothalamus and pituitary has disclosed a high incidence of hypoplasia of the anterior pituitary lobe, attenuation or transection of the pituitary stalk, and formation of an "ectopic" posterior pituitary lobe at the base of the hypothalamus. These anatomic abnormalities may be associated with other congenital malformations of the central nervous system, or may be due to an in utero toxic or infectious insult, perinatal trauma, neonatal asphyxia and hypoxia, head injury, or hemorrhage into a pituitary adenoma. The progressive development of defects in pituitary hormone secretion in such patients is probably due to continued atrophy of an anterior pituitary remnant with a limited vascular supply unstimulated by hypothalamic neuropeptides. By contrast, in patients with isolated hypogonadotropic hypogonadism, hypothalamic pituitary anatomy is normal, although abnormalities of the olfactory sulcus are present in patients with anosmia and hypogonadotropism (Kallmann syndrome). In most patients with central diabetes insipidus, the neurohypophysis is absent on MR scan.

Effect of estrogen on the growth hormone (GH) secretory response to GH-releasing factor in the castrate adult female rat in vivo.

Five groups (n = 11) of 250-g female rats were oophorectomized and immediately thereafter received daily sc injections of estradiol benzoate (EB; 0.05, 0.5, 5.0, and 50.0 micrograms) or vehicle for 28 days. A sixth group underwent sham operation and received injections of vehicle. Somatomedin-C (SmC) concentrations were determined before EB administration. After 4 weeks of EB treatment, the GH response to human GH-releasing factor (1-44) (GRF; 5 micrograms/kg, iv) was determined under pentobarbital anesthesia in seven animals from each group. Serum PRL, LH, and estradiol and plasma SmC concentrations were also measured. The GH secretory response to GRF (delta GH) was greatest in castrated animals receiving vehicle (P less than 0.05) and was significantly blunted in animals receiving 5.0 and 50.0 micrograms EB (P less than 0.05) compared to that in sham-operated animals. A significant negative correlation was observed between delta GH and serum PRL concentrations (r = -0.53; P less than 0.0001). SmC concentrations after treatment were significantly lower in animals receiving 5.0 and 50.0 micrograms EB (P less than 0.01), than in sham-operated animals and were elevated compared to those in sham-operated controls in the group receiving the lowest dose of EB (0.05 microgram; P less than 0.01). Posttreatment SmC levels correlated positively with delta GH (r = 0.58; P less than 0.001) and negatively with serum estradiol concentrations (r = -0.47; P less than 0.01). Pituitary glands from the remaining animals in each group (n = 4) were weighed and assayed for GH, PRL, and LH content. Pituitary PRL content increased with increasing doses of EB replacement and correlated strongly (r = 0.82; P less than 0.0001) with pituitary weight. In the castrated adult female rat, high doses of estrogen inhibited the GH secretory response to GRF in vivo and decreased SmC concentrations. Low dose estrogen increased SmC concentrations, although the GH secretary response to GRF in this group was similar to that in sham-operated rats. The latter observation suggests that the rise in SmC levels associated with low dose estrogen may not be mediated through a change in GH secretion.

Synthesis of 1,25-dihydroxyvitamin D in the nephrectomized pregnant rat.

Pregnant rats were maintained on diets either adequate or deficient in vitamin D. On the 20th day of gestation, animals were either nephrectomized bilaterally or sham operated. Immediately therafter, four groups of nephrectomized or sham-operated pregnant rats received iv [26,27-3H]25-hydroxyvitamin D3 ([26,27-3H]25OHD3), while two groups received [1,2-3H,4-14C]D3. The animals were sacrificed 10-24 h later. The distribution of the radiolabeled metabolites of vitamin D3 was determined in extracts of maternal plasma, maternal intestinal tract, placentae, and fetuses after Sephadex LH-20 column chromatography. Both vitamin D3 and 25OHD3 crossed the placenta and entered the fetus. In anephric animals receiving [26,27-3H]-25OHD3, 24,25-dihydroxyvitamin D and a polar peak eluting in the position of 1,25-dihydroxyvitamin D [1,25(OH)2D] and 25,26-dihydroxyvitamin D were identified in extracts of maternal plasma and intestinal tracts and of placentae and fetuses. The identities of 24,25-dihydroxyvitamin D and 1,25 (OH)2D were confirmed by high pressure liquid chromatography. In rats receiving [1,2-3H,4-14C]D3, approximately 50% of the polar metabolite consisted of 1,25(OH)2D. We conclude that the anephric pregnant rat is able to synthesize 1,25(OH)2D, that the fetal portion of the feto-placental unit is the most likely site of production of this hormone, and that this metabolite of vitamin D is able to cross the placenta from the fetus to the mother.

Hypothyroidism blunts the growth hormone (GH) releasing effect of human pancreatic GH releasing factor in the adult male rat in vivo and in vitro.

The effect of the 44-amino-acid peptide human pancreatic GH releasing factor (hpGRF-44) upon the secretion of GH was studied in control and hypothyroid adult male rats. In animals rendered hypothyroid by ingestion of propylthiouracil (PTU), basal and hpGRF-44-stimulated secretion of GH was depressed in vivo. Administration of T4 together with PTU prevented the decline in basal and hpGRF-provoked GH secretion in vivo. HpGRF-44-stimulated release of rat GH was also impaired in vitro, an effect partially reversed by administration of low doses of T4 in vivo. The depressed in vitro secretion of GH could not be restored in hypothyroidism pituitaries by incubation of the glands with T3. Thus, hypothyroidism blunts hpGRF-44-stimulated secretion of GH in vivo and in vitro in the hypothyroid adult male rat.

Effect of pyridoxine on pituitary release of growth hormone and prolactin in childhood and adolescence.

The dopamine agonist, pyridoxine, was administered to 10 children being evaluated for short stature. Serum GH and PRL responses were contrasted to those after insulin-induced hypoglycemia (ITT) and L-dopa administration. Levels of GH did not change after pyridoxine, but PRL fell (P less than 0.05) to 42% of the zero time concentration. Significant increments of GH occurred during ITT and after L-dopa, while PRL was suppressed to a greater extent by L-dopa. We conclude that pyridoxine is not useful in assessment of hypothalamic-pituitary function.

The response of pituitary gonadotropes to a constant infusion of luteinizing hormone-releasing hormone (LHRH) in normal prepubertal and pubertal children and in children with abnormalities of sexual development.

The pattern of LHRH-evoked release of LH and FSH by pituitary gonadotrophs and the concomitant gonadal steroid secretion were studied in 28 pubertal and 16 prepubertal children. LHRH was administered at doses of 100 mug and 10 mug by a constant-infusion pump over 3 hours following a 2-hour control period. Gonadotropin concentrations were measured at 15-minutes intervals. Mean LH concentrations rose from 2.0 +/- 0.4 (SE) mIU/ml (IRP-2-hMG) to 6.2 +/- 0.9 (P less than .001) in normal prepubertal and from 5.8 +/- 0.9 to 28.0 +/- 3.6 (P less than .001) in normal pubertal children. The peak rise of LH, the mean level attained during the LHRH infusion, and the area under the time-response curve were greater (P less than .001) in pubertal than prepubertal children. The serum LH rise had two components in pubertal children in contrast to a single-phased increase in prepubertal children. Pulsatile release of LH was demonstrated during the basal period in pubertal children and during the LHRH infusion in both groups. FSH release was greater in girls than boys at both stages of pubertal development. A 10 mug LHRH infusion released less LH than did 100 mug in the pubertal children, but more than in prepubertal children. In pubertal boys, plasma testosterone rose (P less than .001) from 222 +/- 45 ng/dl in the control period to 301 +/- 59 following 100 mug LHRH. There was no change in plasma testosterone in the prepubertal boys after 100 mug LHRH or in the pubertal boys following 10 mug LHRH. Plasma estradiol did not rise in girls of either maturity group. In children with hypogonadotropic hypogonadism and structural abnormalities of the hypothalamic-pituitary region, there was no LHRH-evoked gonadotropin release. In 2 agonadal girls, the secretion of LH and FSH was greatly exaggerated. The 3-hour LHRH infusion evoked a maturity-related pituitary LH release and a sex-specific FSH release; a 2-phased pattern of LH secretion was present in pubertal but not in prepubertal children; pulsatile LH release was evoked by the LHRH infusion in prepubertal children.

LH and FSH levels in urine and serum of prepubertal and pubertal children receiving a 3 hour infusion of LH-RH.

LH-RH was administered to 17 normal prepubertal and 14 pubertal children as well as to 6 GH deficient prepubertal patients. Urinary immunoreactive LH and FSH were measured in acetone extracts of 3 h collections prior to, during, and immediately after a 3 h infusion of 100 mug LH-RH. Peak LH excretion in response to LH-RH was higher in pubertal than prepubertal children. Girls excreted larger quantities of FSH after LH-RH than did boys. Serum LH and FSH increments evoked by LH-RH correlated significantly (P less than 0.01) with peak urinary gonadotropin excretion. These data suggest that measurement of urinary immunoreactive LH and FSH prior to and after LH-RH administration is clinically useful in evaluation of the reproductive endocrine system of young children and of individuals with low basal levels of gonadotropin.

Urinary excretion of immunoreactive gonadotropin-releasing hormone-like material in prepubertal and pubertal children.

A urinary product with immunological similarity to Gn-RH has been quantified by radioimmunoassay. The i-Gn-RH-like material apparently has a (partial) structure consistent with the 5 leads to 9 amino acid sequence of hypothalamic Gn-RH. It inhibits the binding of 125I-Gn-RH to anti Gn-RH serum in a manner parallel to synthetic standard, is absorbed by incubation with anti Gn-RH serum, and comigrates with synthetic Gn-RH on Sephadex column chromatography. The concentration of i-Gn-RH-like material is maximal in pubertal males. The total urinary excretion of this substance is two-fold greater in pubertal subjects of both sexes than in prepubertal children. There is no diurnal variation in the excretion of this material. There are significant positive correlations between the urinary content of iGN-RH-like material and LH and FSH. The site of origin, structure and physiological significance of this immunological product remain to be elucidated.

Growth hormone (GH) provocative testing frequently does not reflect endogenous GH secretion.

GH secretion was studied in 73 children with classical GH deficiency or GH neurosecretory dysfunction (GHND), intrinsic short stature, or normal stature. The GH-deficient group was defined by a peak GH secretory response below 10 ng/ml to all provocative tests (arginine, L-dopa, insulin hypoglycemia, and clonidine). GHND was defined by a mean serum 24-h GH concentration below 3 ng/ml, with a normal response (greater than or equal to 10 ng/ml) to provocative testing. Twenty-one GH-deficient children, 21 children with GHND, and 18 short control children underwent provocative GH testing and a 24-h study with GH sampling every 20 min. A group of 13 normal stature control children also underwent 24-h GH sampling. The mean stimulated peak serum GH level [4.7 +/- 0.6 (+/- SEM) ng/ml] in the GH-deficient group was significantly below that in the GHND (19.5 +/- 1.7 ng/ml) and short control groups (24.0 +/- 3.5 ng/ml; P less than 0.01). The mean 24-h serum GH concentration was reduced in GH-deficient (1.5 +/- 0.2 ng/ml) and GHND (2.0 +/- 0.1 ng/ml) children compared to those in short (5.6 +/- 0.5 ng/ml) and normal stature (5.8 +/- 0.8 ng/ml) control children (P less than 0.01). Peak GH concentrations after provocative testing correlated poorly with 24-h mean concentrations in GH-deficient, GHND, and short control children (r = 0.38, 0.23, and 0.41, respectively; P = NS for all groups). Mean serum GH concentrations from blood sampling intervals of 12 h (day/night; 0800-2000/2000-0800 h, respectively) or even 6 h (day; 0900-1500 h) were statistically different in GHND or GH-deficient groups compared to those in control children; however, there was significantly more overlap for individual children using the 6- and 12-h daytime intervals than for the 24-h data. Plasma somatomedin-C/insulin-like growth factor I correlated with mean 24-h GH concentration endogenous secretion (r = 0.7; P less than 0.001). These data suggest that provocative GH testing frequently does not correlate with endogenous GH secretion.