Fcγ-RI, Fcγ-RII and IL-10 as predictive biomarkers for post-therapeutic cicatrization time in monocytes from cutaneous leishmaniasis patients.

Cutaneous leishmaniasis (CL) treatment is based on therapy with Glucantime® , yet, there are few laboratory methods to monitor its success. In this study, ex vivo and in vitro evaluations of peripheral blood monocytes were performed in a longitudinal study to characterize the impact of Glucantime® on overall phenotypic/functional features of these cells from CL patients to identify predictive biomarkers for post-therapeutic monitoring by flow cytometry. The ex vivo evaluation from CL patients demonstrated a modulatory profile before treatment, with a decrease in TLR-2, FcγRII, HLA-DR, CD86, IFN-γR, TNF, IL-12, NO, and an increase in FcγRIII and IL-10R. Conversely, treatment changes some of these biomarker expressions by decreasing FcγRIII and IL-10R and increasing IFN-γR, IL-12 and NO. Moreover, an in vitro analysis of these patients showed a reduced phagocytic capacity of Leishmania braziliensis and higher levels of IL-10 and TGF-ß modulating functional profile. Regardless of the compromised L. braziliensis phagocytic capacity, treatment re-established the production of IL-12, IL-10, TGF-ß and NO at the basal level. Notably, monocytes from patients with early cicatrization showed enhanced FcγRI and FcγRII expressions and reduced IL-10, which was further corroborated by a baseline fold change analysis. Finally, the logistic regression model emphasized the performance of FcγRI, FcγRII and IL-10 as robust predictive biomarkers for post-therapeutic cicatrization during cutaneous leishmaniasis.

Paratuberculosis in Latin America: a systematic review.

Latin America is the definition of the American group, where languages of Latin origin are spoken, including countries in South, Central, and North America. Paratuberculosis is a gastrointestinal contagious chronic disease that affects ruminants, whose etiological agent is the bacilli Mycobacterium avium subsp. paratuberculosis (MAP). Paratuberculosis is characterized by intermittent diarrhea, decreased milk production, dehydration, and progressive weight loss and is possibly involved in Crohn's disease, a human intestinal disease. MAP is resistant to environmental factors, pasteurization, and water disinfection, which coupled with the subclinical-clinical nature of the disease, and makes paratuberculosis a relevant socioeconomic and public health issue, justifying the descriptive review of research on the disease carried out in Latin American countries. A survey of articles, published until September 2016, on the Scopus database, PubMed, Agris, and Science Direct, about detection of the agent and the disease in Latin America, without restrictions to the date of the research was performed. The keywords were as follows: "paratuberculosis," "Mycobacterium avium subsp. paratuberculosis," "cattle," "milk," "wildlife," "goat," "ovine," "dairy," and the name of each country in English. Studies found from nine of the 20 Latin America countries, 31 related to Brazil, 17 to Argentina, 14 to Chile, eight to Colombia, six to Mexico, two to Peru, two to Venezuela, and one to Panama and to Bolivia, each. The agent was detected in cattle, goats, sheep, domesticated water buffalo, and wild animals. Microbiological culture, PCR, and ELISA were the frequent techniques. The small number of studies may result in overestimation or underestimation of the real scenario.

Impact of rare variants in ARHGAP29 to the etiology of oral clefts: role of loss-of-function vs missense variants.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a prevalent, complex congenital malformation. Genome-wide association studies (GWAS) on NSCL/P have consistently identified association for the 1p22 region, in which ARHGAP29 has emerged as the main candidate gene. ARHGAP29 re-sequencing studies in NSCL/P patients have identified rare variants; however, their clinical impact is still unclear. In this study we identified 10 rare variants in ARHGAP29, including five missense, one in-frame deletion, and four loss-of-function (LoF) variants, in a cohort of 188 familial NSCL/P cases. A significant mutational burden was found for LoF (Sequence Kernel Association Test, p = 0.0005) but not for missense variants in ARHGAP29, suggesting that only LoF variants contribute to the etiology of NSCL/P. Penetrance was estimated as 59%, indicating that heterozygous LoF variants in ARHGAP29 confer a moderate risk to NSCL/P. The GWAS hits in IRF6 (rs642961) and 1p22 (rs560426 and rs4147811) do not seem to contribute to the penetrance of the phenotype, based on co-segregation analysis. Our data show that rare variants leading to haploinsufficiency of ARHGAP29 represent an important etiological clefting mechanism, and genetic testing for this gene might be taken into consideration in genetic counseling of familial cases.

Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center

Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.

Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center.

Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.

Short communication: Viable Mycobacterium avium subspecies paratuberculosis in retail artisanal Coalho cheese from Northeastern Brazil.

Mycobacterium avium ssp. paratuberculosis (MAP) is the etiologic agent of paratuberculosis and it potentially plays a role in Crohn's disease. In humans, the main route of transmission of MAP might be the intake of contaminated milk and dairy products. Considering that MAP has already been detected in many types of cheese in different counties, and that Coalho cheese is an important dairy product in northeastern Brazil, the aim of this study was to report the first detection of MAP in retail Coalho cheese in Brazil by PCR and culture. Of 30 retail Coalho cheese samples, 3 (10%) amplified fragments of a similar size to that expected (626 bp) were obtained and viable MAP was recovered by culture from 1 (3.3%) sample. The DNA from the positive culture sample was sequenced and showed 99% identity with the insertion sequence IS900 deposited in GenBank. It was possible to identify the presence of MAP-specific DNA in the analyzed samples for the first time in Brazil, and to recover viable cells from retail Coalho cheese.

Determinants of self-monitoring of blood glucose in patients with Type 1 diabetes: a multi-centre study in Brazil.

AIM: The aim of this study was to determine the relationship between the daily frequency of self-monitoring of blood glucose and glycaemic control, demographic and socio-economic status in patients with Type 1 diabetes under routine clinical care in Brazil. METHODS: This was a cross-sectional, multi-centre study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. The data were obtained from 3176 patients, aged 22 ± 11.8 years, of whom 56.3% were female and 57.4% were Caucasian. The mean time since diabetes diagnosis was 11.7 ± 8.1 years. RESULTS: The prevalence of self-monitoring of blood glucose was 88.5%. There was a significant increase in self-monitoring frequency associated with female gender, lower ages, more intensive diabetes management and higher socio-economic status. A correlation between HbA(1c) levels and the daily frequency of self-monitoring was observed (r(s) = -0.13; P = 0.001). The mean HbA1c levels were related to the daily frequency of self-monitoring (P < 0.001) without additional benefit to patients who performed self-monitoring more than four times daily (9.2, 11.2, 10.2,15.2 and 15% for one, two, three, four, five or more self-monitoring tests daily, respectively; P < 0.0001). CONCLUSIONS: The majority of our patients (88.5%) performed three or more self-monitoring tests daily, with more frequent testing reported by females, younger patients, those on intensive insulin regimens and of higher socio-economic status. No additional benefit was found in patients who performed self-monitoring more than four times daily. The diabetes care team must improve patients' education regarding self-monitoring of blood glucose and its benefits.

Cephalometric analysis of modifications of the pharynx due to maxillo-mandibular advancement surgery in patients with obstructive sleep apnea.

Cephalometry has been used to measure hard and soft facial tissues, as well as the pharyngeal air space for the diagnosis of obstructive sleep apnea (OSA). The changes occurring in the pharynx due to maxillo-mandibular advancement (MMA) have not been established or quantified. The objective of this study was to identify the anatomical changes of the pharynx and of hard tissues that occur in patients with OSA after MMA. 19 patients with a polysomnographic diagnosis of OSA were submitted to cephalometric analysis before and 6 months after surgery in order to evaluate the changes produced by MMA in the pharynx and soft tissues. Cephalometry was standardized in order to obtain descriptive measurements of the dimensions of the airways, the position of the hyoid bone, and maxilla-mandibular relations. The modifications of the pharynx due to MMA showed a significant relation obtained by cephalometry. For each millimeter of maxillary and mandibular bone advancement there was a 0.76mm increase in the retropalatal region and a 1.2mm increase in the pharynx in the retrolingual region. In addition, MMA promoted a significant repositioning of the hyoid bone in the cranial direction.

Short communication: Recovery of viable Mycobacterium avium subspecies paratuberculosis from retail pasteurized whole milk in Brazil.

Mycobacterium avium ssp. paratuberculosis (MAP) is the etiological agent of paratuberculosis, a chronic granulomatous enteritis that affects all ruminants worldwide. Some researchers have indicated a possible role of MAP in Crohn's disease. Despite extensive research and large and important advances in the past few decades, the etiology of Crohn's disease remains indefinite. The most probable transmission route of MAP from animals to humans is milk and dairy products. Mycobacterium avium ssp. paratuberculosis has already been detected in milk samples worldwide, and some studies have reported that MAP is resistant to pasteurization. In Brazil, MAP has been reported in raw milk samples; however, Brazilian retail pasteurized milk has not yet been tested for viable MAP. The aim of this study was to investigate MAP in pasteurized milk in the region of Viçosa (Minas Gerais, Brazil). Thirty-seven samples were collected and processed for culture of MAP. One colony similar to MAP was observed and confirmed by IS900-nested PCR and sequencing. Analysis revealed 97 to 99% identity with the MAP K-10 strain. This study is the first report of the presence of MAP in retail pasteurized whole milk in Brazil.

Characterization of films of weak polyelectrolytes incorporated with poly(vinyl-pyrrolidone)-stabilized gold nanoparticles.

The incorporation process of gold nanoparticles (Au NPs) into self-assembled films was obtained using the layer-by-layer (LbL) technique where two weak polyelectrolytes, i.e., poly(allylamine hydrochloride) (PAH) as polycation and poly(acrylic acid) (PAA) as polyanion, were sequentially adsorbed. To evaluate this process, the films of PAH and PAA were immersed in gold solutions containing different sizes of Au NPs (6 nm and 10 nm) stabilized with poly(vinyl-pyrrolidone) (PVP) before and after treatment with a 0.1 mol L(-1) solution of hydrochloric acid. The systems were analyzed using a multi-method approach involving UV-Visible spectroscopy (UV-Vis), X-ray diffraction (XRD), atomic force (AFM) and transmission electron microscopy (TEM). The results showed that the self-assembled polyelectrolyte films that were not treated by acid showed greater incorporation and better distribution of Au NPs.

Efeito da obesidade sobre as propriedades resistivas e reativas do sistema respiratório / Effect of obesity on the resistive and reactive properties of the respiratory system

A fim de avaliar uma possível relação entre a obesidade e as modificações nas propriedades resistivas e reativas do sistema respiratório e do potencial de oscilações forçadas no estudo da obesidade, mecânica oscilações foram avaliados em 25 saudáveis e 25 indivíduos obesos...

Eletroconvulsoterapia no tratamento da depressao e das manifestaçöes da doença de parkinson / Treatment of parkinson's disease with elctroconvulsive therapy

Mulher, 73 anos, apresenta-se con Doença de Parkinson(DP) em fase avançada sem resposta a medicaçäo classica, associada a quadro depressivo maior. Foi submetida a sete sessöes de ECT com boa toleräncia. A resposta tanto da sintomatologia depressiva quanto das manifestaçöesparkinsonianas (mensurada pela escala de Webster) foi considerada satisfatória. No entanto, a recidiva dos sintomas parkinsonianos e depressivos ocorreu em tempo relativamente curto. Recomendamos que esta modalidade terapêutica seja considerada em pacientes portadores de DP avançada sem resposta à terapêutica clássica principalmente se associada à depress

Evidence for a noncholinergic function of acetylcholinesterase during development of chicken retina as shown by fasciculin.

Fasciculin 2 (FAS), an acetylcholinesterase (AChE) peripheral site ligand that inhibits mammalian AChE in the picomolar range and chicken AChE only at micromolar concentrations, was used in chick retinal cell cultures to evaluate the influence of AChE on neuronal development. The effects of other AChE inhibitors that bind the active and/or the peripheral site of the enzyme [paraoxon, eserine, or 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide (BW284c51)] were also studied. Morphological changes of cultured neurons were observed with the drugs used and in the different cell culture systems studied. Cell aggregates size decreased by more than 35% in diameter after 9 days of FAS treatment, mainly due to reduction in the presumptive plexiform area of the aggregates. Eserine showed no effect on the morphology of the aggregates, although it fully inhibited the activity of AChE. In dense stationary cell culture, cluster formation increased after 3 days and 6 days of FAS treatment. However, FAS, at concentrations in which changes of morphological parameters were observed, did not inhibit the AChE activity as measured histochemically. In contrast, paraoxon treatment produced a slight morphological alteration of the cultures, while a strong inhibition of enzyme activity caused by this agent was observed. BW284c51 showed a harmful, probably toxic effect, also causing a slight AChE inhibition. It is suggested that the effect of an anticholinesterase agent on the morphological modifications of cultured neurons is not necessarily associated with the intensity of the AChE inhibition, especially in the case of FAS. Moreover, most of the effects of AChE on culture morphology appear to be independent of the cholinolytic activity of the enzyme. The results obtained demonstrate that FAS is not toxic for the cells and suggest that regions of the AChE molecule related to the enzyme peripheral site are likely to be involved with the nonclassical role of AChE.

Estado atual dos diuréticos no tratamento da hipertensão arterial sistêmica / Diuretics: actual stage in the treatment of the systemic arterial hypertension

Embora as linhas mestras do tratamento da hipertensão arterial sistêmica variem amplamente em todo o mundo, os diuréticos representam as drogas de primeira linha. Entretanto, o seu uso deve ser extremamente cuidadoso, já que em dose mais elevada determina distúrbios metabólicos que podem agravar o prognóstico.

Growth hormone pulsatility in active and cured acromegalic subjects.

GH secretion in normal subjects is periodic, with pulses prevailing during sleep. During the day (basal secretion), GH levels are, in general, undetectable. We studied GH secretion by cluster analysis, collecting samples every 20 min for 24 h in 44 subjects: 11 patients with active acromegaly; 16 "cured" acromegalics, and 17 normal subjects. The purpose of this study was to compare GH secretion between patients with active acromegaly and "cured" patients and between "cured" acromegalic patients and normal controls. The number of pulses detected through the 24-h GH profile was not different between acromegalic patients regardless of disease activity (17.5 +/- 4.4 vs. 15.0 +/- 6.0, respectively), but was different when active acromegalic patients and normal controls were compared (8.1 +/- 1.0; P < 0.05) and when cured acromegalic patients and normal controls were compared (P < 0.05). The GH pulsatile secretion/total GH secretion ratio was higher in normal controls than in acromegalic patients regardless of disease activity. We concluded that 1) the increases in GH pulsatility in active and cured acromegalic patients are similar, but most of the 24-h GH secretion is nonpulsatile; 2) half of the GH secretion in normal subjects occurs during pulses; 3) cured acromegalic patients, even those with normal GH and insulin-like growth factor I levels, do not recover a normal GH secretory pattern.

Pulsatile growth hormone release in normal women during the menstrual cycle.

OBJECTIVE: We sought to characterize pulsatile growth hormone (GH) release in normal women during the menstrual cycle and to document possible relationships between such characteristics and concentrations of 17 beta-oestradiol and progesterone. SUBJECTS: Fifteen women with ostensibly normal menstrual function were studied during the early follicular phase, 15 during the late follicular phase and 15 during the mid-luteal phase of the menstrual cycle. DESIGN: The phase of the menstrual cycle having been documented, blood samples were obtained from each woman every 10 minutes for 24 hours. MEASUREMENTS: Serum GH was measured in each sample by immunoradiometric assay. Pulsatile GH release was appraised utilizing the objective, statistically-based pulse detection algorithm Cluster. RESULTS: The mean (+/- SEM) integrated serum GH concentration (mU/l min) in late follicular phase women (5335 +/- 848) was higher than that observed in early follicular phase women (3156 +/- 322; P = 0.032). The integrated GH concentration calculated for mid-luteal phase women (3853 +/- 788) was intermediate between but not statistically different from that observed in early follicular (P = 0.48) and late follicular (P = 0.14) phase women. No differences in GH pulse frequency (pulses/24 hours) were found among early follicular (8.27 +/- 0.55), late follicular (7.93 +/- 0.91) or mid-luteal (8.47 +/- 0.66) phase women. Mean maximal GH pulse amplitude (mU/l) was higher in late follicular phase (8.93 +/- 1.00) than early follicular phase (5.74 +/- 0.67; P = 0.008) and mid-luteal phase (5.76 +/- 0.74; P = 0.008) women. Similarly, incremental GH pulse amplitude (mU/l) was higher in late follicular phase (7.33 +/- 0.83) than early follicular phase (4.68 +/- 0.58; P = 0.005) and mid-luteal phase (4.36 +/- 0.39; P = 0.002) women. No differences in mean pulse widths or in the interpeak valley mean GH concentrations were found among the groups. Multiple regression of each pulse parameter against serum concentrations of testosterone, 17 beta-oestradiol and progesterone revealed a significant (P = 0.045) positive correlation between maximum GH pulse amplitude and oestradiol and a significant (P = 0.04) negative correlation between maximal GH pulse amplitude and progesterone (r = 0.41). CONCLUSION: These results suggest that late follicular phase concentrations of oestradiol may enhance circulating GH via an amplitude-modulated rather than a frequency-modulated effect on the endogenous GH pulse. Progesterone may blunt this oestrogen-associated effect, thus resulting in the observed mid-luteal phase concentrations of GH. Whether these gonadal hormones act primarily at the hypothalamus and/or anterior pituitary gland remains to be clarified, but the present observations indicate that pulsatile GH release throughout the normal menstrual cycle is significantly amplitude regulated.

Temporal structure of in vivo growth hormone secretory events in humans.

The time course of spontaneous growth hormone (GH) secretion was studied in 12 normal men by analyzing serum GH concentrations measured in blood collected at 5-min intervals over 24 h with a multiple-parameter deconvolution model to simultaneously resolve endogenous GH secretory and clearance rates. Twenty-four-hour profiles of serum GH concentrations were accounted for by an average of 12 +/- 1.2 (SE) discrete GH secretory bursts having a mean half-duration (duration at half-maximal amplitude) of 25 +/- 2.3 min, indicating that 95% of daily GH secretion occurred in 8.8 h. The majority (96%) of GH was secreted in volleys composed of multiple (4.0 +/- 0.4) discrete secretory bursts. Such volleys of GH secretion were separated by 171 +/- 19 min, whereas their constituent individual secretory events occurred every 36 +/- 1.7 min (P = 0.0001). Between secretory volleys, calculated GH secretory rates fell asymptotically to zero. Significant positive and negative autocorrelations were observed for the series consisting of successive GH secretory burst mass and interburst intervals, respectively. Linear regression analysis revealed significant negative correlations between the mass of GH secreted per burst and both the preceding and following interburst intervals. Estimates of the half-life of endogenous GH (17 +/- 1.7 min) and of the endogenous GH production rate (0.25 +/- 0.033 mg/m2 for an assumed distribution volume of 7.9% body wt) agreed well with earlier independent measurements. We conclude that the human pituitary gland secretes GH in volleys consisting of multiple secretory bursts, without measurable intervening tonic secretion. This pattern of in vivo GH release in normal humans is consistent with a model of high-frequency GH-releasing hormone secretory events superimposed on low-frequency episodes of somatostatin withdrawal.

Somatotropin pulse frequency and basal concentrations are increased in acromegaly and are reduced by successful therapy.

Alterations in pulsatile GH release in 13 acromegalic patients (7 men and 6 women) were studied by measuring serum GH concentrations in blood sampled every 5 min over 24 h. Specific properties of pulsatile GH release were quantitated by Cluster analysis, and Fourier expansion time series analysis was used to resolve fixed periodicities underlying GH secretion. Compared with sex-matched controls, 24-h integrated GH concentrations (IGHC; min.mg/L) were elevated 15-fold in the acromegalic men (40 +/- 27 vs. 2.6 +/- 0.35; P = 0.02) and 10-fold in the acromegalic women (43 +/- 19 vs. 4.1 +/- 0.35; P = 0.01). The increase in integrated GH concentrations was accounted for by an increase in the nonpulsatile fraction [men, 31 +/- 20 vs. 0.65 +/- 0.10 (P = 0.001); women, 35 +/- 14 vs. 1.2 +/- 0.10 (P = 0.0008)]; the pulsatile component was not different from that in normal subjects. Acromegalics had an increased number of pulses per 24 h [men, 17 +/- 1.5 vs. 6.7 +/- 1.4 (P = 0.0001); women, 19 +/- 1.6 vs. 11 +/- 1.0 (P = 0.002)] and increased basal GH concentrations [men, interpulse valley mean, 22 +/- 14 vs. 1.4 +/- 0.30 micrograms/L (P = 0.0006); women, 27 +/- 12 vs. 1.3 +/- 0.20 micrograms/L (P = 0.0001)]. The proportion of the mean GH concentration attributable to 24-h rhythmicity was decreased in the acromegalic patients. Five patients studied during biochemical remission (4 after transsphenoidal surgery and 1 during bromocriptine therapy) had GH profiles that resembled those of normal subjects. Pulsatile GH secretion in acromegaly is characterized by augmented basal GH concentrations, increased GH pulse frequency, and an attenuation of the underlying 24-h rhythm. Such a pattern may be secondary to the intrinsic pathology of adenomatous somatotrophs and/or the effects of altered hypothalamic regulation.

Alterations in the pulsatile mode of growth hormone release in men and women with insulin-dependent diabetes mellitus.

The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin-dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion time-series analysis. Compared to those in age-matched controls, integrated 24-h concentrations of GH were 2- to 3.5-fold higher in diabetic men (P = 0.002) and women (P = 0.0005). Both men and women with DM had over 50% more GH pulses per 24 h than their non-DM counterparts. In addition, maximal GH pulse amplitude was markedly elevated in the men and women with DM (P = 0.0019 and 0.0189, respectively). That the increase in maximal pulse amplitude was accounted for by greater baseline levels was documented by a higher interpulse valley mean GH concentration in the diabetics compared to the controls (P = 0.0437 and 0.0056, men and women, respectively) and the absence of any difference in incremental pulse amplitude for either sex (P greater than 0.05). DM men had larger GH pulse areas (P = 0.039) than control men, apparently accounted for by greater pulse width (P = 0.0037). Pulse areas in DM and non-DM women were indistinguishable. Time-series analysis revealed that the 24-h (circadian) rhythms of serum GH concentrations exhibited significantly increased amplitudes in the diabetic group as a whole (compared to the controls, P = 0.011). However, the times of maximal GH concentrations (acrophases) were not significantly different. As a group, serum insulin-like growth factor-I was lower in DM vs. non-DM individuals (P = 0.0014), although when separated by sex this difference did not reach statistical significance in women (P = 0.317). The present data confirm the higher circulating levels of GH previously reported to occur in individuals with poorly controlled DM. The altered frequency of GH pulses together with enhanced interpulse GH concentrations and an amplified circadian GH rhythm are compatible with hypothalamic dysfunction associated with dysregulation of somatostatin and/or GHRH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)