Post-operative volumes following endoscopic surgery for non-functioning pituitary macroadenomas are predictive of further intervention, but not endocrine outcomes.

BACKGROUND: Transsphenoidal surgery (TSS) remains the treatment of choice for non-functioning pituitary macroadenomas (NFPMA). The value of measuring tumour volumes before and after surgery, and its influence on endocrine outcomes and further treatment of the residual or recurrent tumour are unknown. METHODS: Data from patients who underwent endoscopic TSS for a NFPMA (2009-2018) in a UK tertiary centre were analysed for pre- and post-operative endocrine and surgical outcomes. RESULTS: Of 173 patients with NFPMA, 159 (61% male) were treatment naïve. At presentation, 76.2% (77/101) had ≥1 pituitary axis deficit. Older age (p = 0.002) was an independent predictor for multiple hormonal deficiencies. Preoperative tumour volume did not correlate with degree of hypopituitarism. Postoperative tumour volume and extent of tumour resection were not predictive of new onset hypopituitarism. Hormonal recovery was observed in 16 patients (20.8%) with impaired pituitary function, with the greatest recovery in the hypothalamic-pituitary-adrenal axis (21.2%, 7/33). A larger residual tumour volume was predictive of adjuvant radiotherapy (3.40 vs. 1.24 cm3, p = 0.005) and likelihood for repeat surgery (5.40 vs. 1.67cm3, p = 0.004). CONCLUSION: Pre- and post-operative NFPMA volumes fail to predict the number of pituitary hormone deficits, however, greater post-operative residual volumes increase the likelihood of further intervention to control tumour growth.

High-level association of bovine digital dermatitis Treponema spp. with contagious ovine digital dermatitis lesions and presence of Fusobacterium necrophorum and Dichelobacter nodosus.

Contagious ovine digital dermatitis (CODD) is an important foot disease in sheep, with significant animal welfare and economic implications. It is thought that CODD emerged from bovine digital dermatitis (BDD) via treponemal bacteria. With wildlife species such as elk now suffering a CODD-like disease, it is imperative to clarify these disease etiologies. A large investigation into treponemal association with CODD is warranted. CODD lesions (n = 58) and healthy sheep foot tissues (n = 56) were analyzed by PCR for the three BDD-associated Treponema phylogroups and two other lameness-associated bacteria, Dichelobacter nodosus and Fusobacterium necrophorum. Spirochete culture was also attempted on CODD lesions. "Treponema medium/Treponema vincentii-like," "Treponema phagedenis-like," and Treponema pedis spirochetes were identified in 39/58 (67%), 49/58 (85%), and 41/58 (71%) of CODD lesions, respectively. One or more BDD-associated Treponema phylogroups were detected in 100% of CODD lesions. Healthy foot tissues did not amplify BDD-associated Treponema phylogroup DNA. D. nodosus and F. necrophorum were present in 34/58 (59%) and 41/58 (71%) of CODD lesions and 22/56 (39%) and 5/56 (9%) of healthy foot tissues, respectively. Thirty-two spirochetes were isolated from CODD lesions, with representatives clustering with, and indistinguishable from, each of the three BDD-associated Treponema phylogroups based on 16S rRNA gene comparisons. This study for the first time demonstrates a high-level association for BDD treponeme phylogroups in CODD and their absence from healthy tissues, supporting the hypothesis that BDD treponemes play a primary causative role in CODD and confirming that the specific PCR assays are an effective differential diagnostic tool for CODD.

Antimicrobial resistance in some gram-negative bacteria isolated from the bovine ejaculate.

The bacterial load and degree of antibiotic resistance present in untreated and antibiotic-treated semen samples were investigated in five bulls standing at a cattle-breeding centre. Bacterial load was determined by colony counts from semen samples cultured on brain heart infusion and nutrient agar plates. Antibiotic resistance in these bacteria was assessed by measuring the diameter of bacterial growth inhibition zones around discs containing different concentrations of antibiotics. Representative antibiotic-resistant bacterial isolates were selected for identification. Untreated semen contained few culturable bacteria, and all were completely sensitive to gentamycin, spectinomycin and lincomycin: six of the isolates showed some resistance to tylosin. In semen to which antibiotics had been added as part of the routine production process, two isolates were sensitive to all of the antibiotics tested, and the remainder were resistant to all. Resistant Gram-negative isolates that were identified included Pseudomonas and Stenotrophomonas spp. both in the class Gammaproteobacteria and a Sphingomonas sp. which is in the class Alphaproteobacteria.

Epidemiology of bovine venereal campylobacteriosis: geographic distribution and recent advances in molecular diagnostic techniques.

Bovine venereal campylobacteriosis (BVC) is a major cause of economic loss to the cattle industries in different parts of the world. Camplylobacter fetus subsp. venerealis (Cfv), the main causative agent of BVC, is highly adapted to the genital tract of cattle and is transmitted by carrier bulls. However, infertility and abortions can also be caused by the intestinal pathogens C. fetus subsp. fetus (Cff), and C. jenuni, which are not venereally transmitted. Bovine venereal campylobacteriosis, caused by Cfv associated with lowered fertility, embryo mortality and abortion, repeated returns to service, reduced pregnancy rates and extended calving intervals, has the highest prevalence in developing countries where natural breeding in cattle is widely practised. The epidemiology, pathogenesis and diagnosis of the disease have been the subject of previous reviews. The main focus of this review is to highlight the epidemiology of this disease with particular reference to geographical distribution and recent advances in molecular diagnostic techniques. It is hoped that further research interest of scientists will be stimulated with a view to finding lasting solutions to the reproductive problems associated with the disease for better livestock productivity, particularly in developing endemic countries.

Can We Discharge Dynamically Risk-Stratified Low-Risk (Excellent Response to Treatment) Thyroid Cancer Patients After 5 Years of Follow-Up?

AIMS: The 2014 British Thyroid Association thyroid cancer guidelines recommend lifelong follow-up of thyroid cancer patients. This is probably unnecessary, can cause patient anxiety, is time consuming and places significant demand on National Health Service resources. It has been suggested that low-risk differentiated thyroid cancer (DTC) patients could be discharged to primary care once they are 5 years from diagnosis and treatment. The aim of this study was to investigate the potential safety of this practice. MATERIALS AND METHODS: In total, 756 patients with dynamically risk-stratified (DRS) low-risk/excellent response to treatment DTC treated over 2001-2013 in the Leeds region were followed after diagnostic surgery and the recurrence rate calculated. RESULTS: The median follow-up time was nearly 10 years (5-17 years). Radiological recurrence occurred in 13/756 (1.7%) patients and was always preceded by raised thyroglobulin/ thyroglobulin antibody levels. In all 13 patients elevation of thyroglobulin occurred within 5 years of diagnosis. Two additional patients were found to have rising thyroglobulin at almost 9 and 10.5 years from diagnosis, although to date radiological recurrence has not been detected. Assuming these two patients developed recurrence with longer duration of follow-up, then 0.26% (2/756) of patients would not have their recurrence discovered within 5 years of diagnosis. To detect 100% of patients with a putative recurrence in our cohort would require 10.5 years of follow-up. Four patients had transiently raised thyroglobulin, which became undetectable within 2 years (in three patients), without any treatment and radiological recurrence was not discovered. CONCLUSION: Discharge of DRS low-risk DTC patients to primary care after 5 years of secondary care follow-up is reasonable, accepting that late recurrence may occur in a very small minority of individuals (0.26%, ∼1:400). A more cautious approach would be to continue monitoring for 10 years, although the frequency of assessments could be reduced with increasing duration of follow-up.

The immune status of the bovine uterus during the peripartum period.

The post-partum period in cattle is characterised by an increased risk of infection of the uterus, as the anatomical barriers are broached during parturition and remain open for several days. Infection of the uterus is largely influenced by the balance between bacterial contamination and the local and systemic immune status during pregnancy and around parturition. Infectious diseases are more prevalent during this period, because of an impaired immune status before and immediately after parturition. Neutrophils play a primary role in the defence of the uterus against infection. Influx of neutrophils into the uterus is thought to be mediated by chemoattractants, chemokines and adhesion molecules, such as beta2-integrin (complement receptor 3) and L-selectin (CD62L). Other cellular components activated in the uterus during this period include lymphocytes, eosinophils, mast cells and macrophages. The major classes of immunoglobulins (IgM, IgA and IgG), either by passive diffusion or local production, play an important protective role in the uterus by acting as opsonins to enhance phagocytosis, stimulating the complement pathways or blocking pathogens from adhering to mucosal surfaces. Endometrial cells express toll-like receptor 4 (TLR4), which recognises lipopolysaccharides of Escherichia coli and other Gram negative bacteria, the most common causes of bovine endometritis. Activation of TLR4 triggers the production of tumour necrosis factor alpha and other pro-inflammatory cytokines. The periparturient period is also characterised by an increased secretion of prostaglandin F(2alpha), which enhances uterine immune defences.

Field investigation of perinatal mortality in friesian cattle associated with myocardial degeneration and necrosis.

Perinatal mortality and stillbirths were investigated in an extensively managed herd of Friesian cows and heifers calving over a 2-year period: 504 cows were calved and 215 heifers. Cows were bred to Friesian and Jersey bulls using natural service. The perinatal fetal mortality rate was 7.5% for cows and 30% for heifers. An experienced stockman managed these calvings and veterinary assistance was required only on nine occasions. All stillborn fetuses were examined post-mortem by the Veterinary Laboratories Agency, Carmarthen and no infectious agent was identified on any occasion. Thyroid hyperplasia was found in two fetuses. In blood samples taken from 10 late pregnant heifers, mean glutathione peroxidase values were 7.9 +/- 1.7 IU/ml Packed Cell Volume (PCV). Tissues from eight fetuses were submitted to the University of Liverpool for histopathological examination; all presented lesions consistent with myocardial degeneration and necrosis of the left ventricle. Following treatment of 205 late pregnant heifers with sodium selenite and vitamin E, the overall perinatal mortality rate in these cattle fell to below 11%.

Historical and current perspectives on the treatment, control and pathogenesis of milk fever in dairy cattle.

Milk fever has been recognised in cattle for about 215 years and its clinical signs have not changed since they were described by Victorian veterinary surgeons in the mid-nineteenth century. It was only 80 years ago that abnormal parathyroid gland function was associated with the pathogenesis of the hypocalcaemia characteristic of the disease, and the current basis for its treatment with intravenous calcium salts was established. Although this treatment is effective, most recent research has focused on preventing the disease through an understanding of the endocrine control of extracellular calcium homeostasis. In the 1970s the synthetic vitamin D analogue 1alpha-hydroxycholecalciferol was developed for intramuscular injection before a cow calved, but variable results encouraged other preventive strategies to be considered, including restricting the dietary intake of calcium, and manipulating the dietary cation-anion balance of cows before they calved. Currently, the role of extracellular calcium receptors in the parathyroid gland is under investigation as a preliminary step to devising more effective treatments and/or preventive methods for milk fever.

Possible role of adenosine in the macula densa mechanism of renin release in rabbits.

This study was designed to examine: (a) the effects of adenosine and its analogues on renin release in the absence of tubules, glomeruli, and macula densa, and (b) whether adenosine may be involved in a macula densa-mediated renin release mechanism. Rabbit afferent arterioles (Af) alone and afferent arterioles with macula densa attached (Af + MD) were microdissected and incubated for two consecutive 30-min periods. Hourly renin release rate from a single arteriole (or an arteriole with macula densa) was calculated and expressed as ng AI X h-1 X Af-1 (or Af + MD-1)/h (where AI is angiotensin I). Basal renin release rate from Af was 0.69 +/- 0.09 ng AI X h-1 X Af-1/h (means +/- SEM, n = 16) and remained stable for 60 min. Basal renin release rate from Af + MD was 0.20 +/- 0.04 ng AI X h-1 X Af + MD-1/h (n = 6), which was significantly lower (P less than 0.0025) than that from Af. When adenosine (0.1 microM) was added to Af, renin release decreased from 0.72 +/- 0.16 to 0.24 +/- 0.04 ng AI X h-1 X Af-1/h (P less than 0.025; n = 9). However, when adenosine was added to Af + MD, no significant change in renin release was observed. N6-cyclohexyl adenosine (an A1 adenosine receptor agonist) at 0.1 microM decreased renin release from Af from 0.69 +/- 0.14 to 0.39 +/- 0.12 ng AI X h-1 X Af-1/h (n = 5, P less than 0.05). However, 5'-N-ethylcarboxamide adenosine (an A2 adenosine receptor agonist) either at 0.1 microM or at 10 microM had no effect. Theophylline, at a concentration (10 microM) that does not block phosphodiesterase but does block adenosine receptors, increased renin release from Af + MD from 0.21 +/- 0.03 to 0.46 +/- 0.08 ng AI X h-1 X Af + MD-1/h (P less than 0.05; n = 8). The results are consistent with the hypotheses that adenosine decreases renin release via the activation of A1 adenosine receptors, and that adenosine may be an inhibitory signal from the macula densa to juxtaglomerular cells.

Endemic goitre and hypothyroidism in an adult female patient dependent on total parenteral nutrition.

We present the case of a thirty-year-old female patient who was referred to the endocrinology team with an enlarging goitre and biochemical hypothyroidism. She had been dependent on total parenteral nutrition for the previous six years as a result of intestinal failure thought to be caused by possible underlying mitochondrial disease. The patient also suffers from a Desmin myopathy, and at present, the exact aetiology behind her intestinal failure is not certain. The goitre was smooth and had been enlarging slowly over the previous few months. Thyroid peroxidase antibodies were found to be within normal range. Further analysis of the case showed that twelve months earlier the patients total parenteral nutrition (TPN) feed had been altered as a result of manganese toxicity. The current feeding regimen did not contain a trace element additive which had previously supplied iodine supplementation. A little detective work established that iodine content to the TPN had been reduced, the trace element additive (Additrace) was recommenced providing 1 µmol of iodine per day, equating to 130 µg of iodine. Following this change, thyroid-stimulating hormone levels returned to normal and the goitre quickly reduced in size. We present a rare case of endemic goitre and hypothyroidism in a patient receiving inadequate iodine supplementation through total parenteral nutrition. LEARNING POINTS: Endemic goitre and hypothyroidism secondary to iodine deficiency are rare in the developed world. However, the diagnosis should be considered in the setting of a diffuse goitre and negative thyroid antibodies.Although rare, endemic goitre should be considered in patients who present with hypothyroidism and who are dependent on total parenteral nutrition.Treatment with levothyroxine is not required in endemic goitre as thyroid function tests generally normalise with the addition of iodine to the diet/total parenteral nutrition regimen.Iodine supplementation at a level recommended by the European Society for Clinical Nutrition and Metabolism (ESPEN) was observed to quickly normalise this patient's thyroid function tests.

A stereological method for estimating the feto-maternal exchange surface area in the bovine placentome at 135 days gestation.

The feto-maternal relationships within the bovine placentome at 135 days gestation were investigated using unbiased stereology. This provides an estimate of the feto-maternal interface without physically separating these. The functional surface area, the volume of the fetal and maternal components, volumetric tissue shrinkage due to processing, and the feto-maternal surface amplification factor were estimated and quantified in standard units. In this healthy bovine pregnancy there were 105 placentomes with a total volume of 900 ml. The volumetric tissue shrinkage was 24% and the maternal: fetal tissue ratio overall was 0.92. The total feto-maternal exchange surface area was 18.5 m2 with a surface amplification factor of 108.1. Analysis of the coefficient of error from counting different numbers of points within the reference area suggested that 50% and 75% fewer points could be counted to achieve the result obtained by counting approximately 6000 points used in this study.

Bovine digital dermatitis: Current concepts from laboratory to farm.

Bovine digital dermatitis (DD) is a severe infectious disease causing lameness in dairy cattle worldwide and is an important ruminant welfare problem that has considerable economic issues. Bovine DD is endemic in many regions worldwide and it is important to understand this major disease so that effective control strategies can be identified. There is substantial evidence that specific treponeme phylotypes play an important causative role in bovine DD. This review considers current research, including DD Treponema spp. investigations, associated DD pathobiology, and current and potential treatment and control options. Epidemiological data, alongside new microbiological data, help delineate important transmission routes and reservoirs of infection that allow effective interventions to be identified. Better on-farm housing hygiene, pasture access, routine footbathing and claw trimming with disinfected equipment need to be implemented to significantly reduce the incidence of DD. There is a paucity of peer reviewed research into both commonly used and novel treatments. In vitro antimicrobial susceptibility studies of DD treponemes and effective treatment of human treponematoses clearly indicate that antibiotics frequently selected for DD treatments are not the most efficacious. Whilst there are understandable concerns over milk withdrawal times in dairy cattle, more needs to be done to identify, license and implement more appropriate antibiotic treatments, since continued overuse of less efficacious antibiotics, applied incorrectly, will lead to increased disease recurrence and transmission. More research is needed into methods of preventing DD that circumvent the use of antibiotics, including vaccination and transmission blocking studies, to reduce or hopefully eradicate DD in the future.

Role of transesophageal echocardiography-guided cardioversion of patients with atrial fibrillation.

Electrical cardioversion of patients with atrial fibrillation (AF) is frequently performed to relieve symptoms and improve cardiac performance. Patients undergoing cardioversion are treated conventionally with therapeutic anticoagulation for three weeks before and four weeks after cardioversion to decrease the risk of thromboembolism. A transesophageal echocardiography (TEE)-guided strategy has been proposed as an alternative that may lower stroke and bleeding events. Patients without atrial cavity thrombus or atrial appendage thrombus by TEE are cardioverted on achievement of therapeutic anticoagulation, whereas cardioversion is delayed in higher risk patients with thrombus. The aim of this review is to discuss the issues and controversies associated with the management of patients with AF undergoing cardioversion. We provide an overview of the TEE-guided and conventional anticoagulation strategies in light of the recently completed Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) clinical trial. The two management strategies comparably lower the patient's embolic risk when the guidelines are properly followed. The TEE-guided strategy with shorter term anticoagulation may lower the incidence of bleeding complications and safely expedite early cardioversion. The inherent advantages and disadvantages of both strategies are presented. The TEE-guided approach with short-term anticoagulation is considered to be a safe and clinically effective alternative to the conventional approach, and it is advocated in patients in whom earlier cardioversion would be clinically beneficial.

Difference in the respiratory variation between pulmonary venous and mitral inflow Doppler velocities in patients with constrictive pericarditis with and without atrial fibrillation.

OBJECTIVES: The goal of this study was to evaluate the difference in the respiratory change from expiration to inspiration (%E) between pulsed Doppler mitral inflow (MV) and pulmonary venous flow (PV) velocities in patients with constrictive pericarditis (CP) and to describe the influence of atrial fibrillation (AF). BACKGROUND: The difference in %E between MV and PV velocities as well as the influence of AF on %E has not been well described. METHODS: Pulsed-wave Doppler transesophageal echocardiography (TEE) was performed with respiratory monitoring in 31 patients with CP and sinus rhythm (SR) and in 10 patients with CP and AF. The MV early (E) and late diastolic (A) velocities and their velocity time integral (VTI) as well as PV systolic (S) and diastolic (D) velocities and their VTI were measured. RESULTS: Regardless of the cardiac rhythm: 1) The MV-E velocity and E-VTI as well as PV-D velocity and D-VTI significantly decreased from expiration to inspiration; 2) the %E in PV-D velocity (27% in SR and 35% in AF) and D-VTI (38% in SR and 45% in AF) was significantly greater than that in MV-E velocity (18% in SR and 15% in AF) and E-VTI (21% in SR and 19% in AF), respectively; 3) the PV S/D and S/D-VTI significantly increased from expiration to inspiration. CONCLUSIONS: A significant respiratory variation was observed in both MV and PV velocities in CP, not only in patients with SR but also in those with AF. Moreover, the %E was greater in the PV velocities than it was in the MV velocities. Evaluation of the %E in the PV velocities using TEE can be a sensitive diagnostic strategy for evaluation of patients with CP, even in patients with AF.

Reliability of echocardiographic measurements of myocardial perfusion using commercially produced sonicated serum albumin (Albunex).

OBJECTIVES: The purpose of this study was to assess the reproducibility and pitfalls of intracoronary and aortic root sonicated albumin injections, using time-intensity curves, in a large sample of normal dogs. BACKGROUND: The utility of a new myocardial contrast echocardiographic agent, sonicated serum albumin (Albunex), is currently under investigation. However, the reproducibility, injection techniques and general pitfalls of this contrast agent have not been well characterized. METHODS: We administered sequential intracoronary and aortic root injections (518 injections) of sonicated albumin in 25 closed chest normal dogs to measure the effectiveness and reproducibility of this product. Time-intensity curves, as a measure of myocardial perfusion, were derived and quantified using an on-line videodensitometric analysis system and two-dimensional echocardiography. Measurements included peak intensity, area under the curve, half-time of descent, alpha-parameter and transit time within a 31- x 31-pixel "region of interest" in the anterior septum. Analyses provided 80% power and a type I error protection of 95%. RESULTS: The best reproducibility of the variables was half-time of descent for aortic root injections (coefficient of variation [CV] 20%) and peak intensity for intracoronary injections (CV 25%), whereas aortic root area under the curve showed the most variability (CV 41%). Analysis of variance for repeated measures of serial intracoronary and aortic root injections showed no significant systematic variability within subjects for the measured variables. In a comparison between intracoronary and aortic root injection sites, paired t tests showed no significant difference for mean values between these two techniques. There was also no statistically significant difference between manual versus power intracoronary injections. Finally, there was no significant difference among three injection rates (1, 2 and 3 ml/s) in paired intracoronary injections, nor was there a difference among injection rates in paired aortic root injections, except for a lower peak intensity with a 1-ml/s injection rate compared with a 2-ml/s injection rate (p = 0.01). Potential pitfalls include preparation of sonicated albumin, delivery techniques and measurement variables. CONCLUSIONS: We conclude that the results of serial injections of sonicated albumin show no systemic change or trend in normal dogs. Both intracoronary and aortic root injections at standard injection rates by hand or power injector can be used to quantify time-intensity curves, as measure of myocardial perfusion, with similar variability ranging from 20% to 41%. These results are important in the human model, especially after coronary interventions.

Integrated backscatter for quantification of left atrial spontaneous echo contrast.

OBJECTIVES: This study was designed to develop a quantitative method of spontaneous echo contrast (SEC) assessment using integrated backscatter and to compare integrated backscatter SEC measurement with independent qualitative grades of SEC and clinical and echocardiographic predictors of thromboembolism. BACKGROUND: Left atrial SEC refers to dynamic swirling smokelike echoes that are associated with low flow states and embolic events and have been graded qualitatively as mild or severe. METHODS: We performed transesophageal echocardiography in 43 patients and acquired digital integrated backscatter image sequences of the interatrial septum to internally calibrate the left ventricular cavity and left atrial cavity under different gain settings. Patients were independently assessed as having no, mild or severe SEC. We compared intensity of integrated backscatter in the left atrial cavity relative to that in the left ventricular as well as to the independently assessed qualitative grades of SEC. Fourier analysis characterized the temporal variability of SEC. The integrated backscatter was compared with clinical and echocardiographic predictors of thromboembolism. RESULTS: The left atrial cavity integrated backscatter intensity of the mild SEC subgroup was 4.7 dB higher than that from the left ventricular cavity, and the left atrial intensity of the severe SEC subgroup was 12.5 dB higher than that from the left ventricular cavity. The left atrial cavity integrated backscatter intensity correlated well with the qualitative grade. Fourier transforms of SEC integrated backscatter sequences revealed a characteristic dominant low frequency/high amplitude spectrum, distinctive from no SEC. There was a close relationship between integrated backscatter values and atrial fibrillation, left atrial size, left atrial appendage flow velocities and thrombus. CONCLUSIONS: Integrated backscatter provides an objective quantitative measure of SEC that correlates well with qualitative grade and is closely associated with clinical and echocardiographic predictors of thromboembolism. The relationship between integrated backscatter measures and cardioembolic risk will be defined in future multicenter studies.

Vasopressin and vascular reactivity in the development of DOCA hypertension in rats with hereditary diabetes insipidus.

To examine the role of vasopressin (VP) in DOCA-salt hypertension, arterial pressure and renal vascular reactivity were studied in control Long-Evans (LE) rats and in Brattleboro rats homozygous for diabetes insipidus (DI rats). Vascular reactivity to norepinephrine, VP and angiotensin II was assessed in isolated kidneys perfused at constant flow. LE rats showed an increase in arterial pressure (AP) which was significant at 2 weeks post DOCA and averaged 180 mm Hg at 4 weeks. DI rats lacking VP showed no rise in AP after DOCA; however, DI rats given VP and DOCA developed hypertension with a course and magnitude similar to that observed in LE rats. At 6 to 10 weeks post DOCA, renal vascular reactivity to all agents was increased in LE rats and DI rats replaced with VP. Normotensive DI rats lacking VP showed depressed reactivity. Assessment of changes in reactivity at 3 days post DOCA showed that changes preceded the rise in AP. These data suggest that VP may play a primary role in the pathogenesis of DOCA hypertension and that its mechanism may involve an induction of increased vascular reactivity.

GH-deficient survivors of childhood cancer: GH replacement during adult life.

Childhood survivors of cancer are prone to a number of adverse sequelae related to the therapeutic interventions undertaken to achieve remission. The endocrine system is frequently affected; hypothalamo-pituitary dysfunction, in particular GH deficiency, is common after cranial irradiation. It is unclear to what extent GH deficiency contributes to the abnormalities observed in adult survivors of childhood cancer, and whether GH replacement reverses these anomalies. We compared 27 GH-deficient survivors of childhood cancer with 27 adult age- and sex-matched controls and went on to replace GH in the patient group to determine whether GH resulted in improvements of the baseline abnormalities. The GH-deficient survivors of childhood cancer had an adverse lipid profile (total cholesterol, 5.4 vs. 4.6 mM, P = 0.004; high-density lipoprotein cholesterol, 1.05 vs. 1.6 mM, P < 0.001; and triglycerides, 1.3 vs. 1.0 mM, P < 0.001) and were osteopenic (lumbar spine z-score, -1.53 vs. -0.31 SD score, P < 0.001; femoral neck z-score, -1.23 vs. -0.27 SD score, P = 0.02); additionally, the female subgroup had an increased percentage body fat (43.6 vs. 32.8%, P = 0.016). In keeping with the selection criterion, quality of life in the patient cohort, relative to the healthy controls, was severely impaired [adult GH-deficiency assessment (AGHDA), 15.5 (range, 8-25) vs. 1 (range, 0-19), P < 0.0001; psychological general well-being schedule, 67.5 (range, 18-86) vs. 89.0 (range, 51-104), P < 0.0001]. After 12 months of GH replacement, small (but significant) improvements were observed in body composition in the male subgroup (waist-hip ratio, 0.871 vs. 0.863, P < 0.05); and in the female cohort, total cholesterol (6.0 vs. 5.2 mM, P = 0.01) and triglyceride (2.1 vs. 1.4 mM, P = 0.01) levels fell. Bone mineral density improved in only one of the four sites studied (ultradistal radius, -1.21 vs. -1.09, P = 0.048) after a median duration of GH therapy of 18 months. Quality of life improved dramatically by 3 months (AGHDA, 15.5 vs. 10.0, P < 0.001), and the improvement was maintained at 12 months (AGHDA, 15.5 vs. 9.0, P < 0.001). Importantly, there was no clinical suggestion of tumor recurrence during the 12 months of GH replacement. The minor improvements observed in body composition, the lipid profile, and bone mineral density in GH-deficient adult survivors of childhood cancer after 12-18 months of physiological GH replacement suggest that GH deficiency may not be the major etiological factor in their pathogenesis; the converse seems to be true for the quality of life status of these individuals. We propose that, as in patients with hypopituitarism caused by pituitary disease, the main indication for GH replacement in GH-deficient survivors of childhood cancer should be severe impairment of quality of life.

Comparative absorption of [13C]glucose and [13C]lactose by premature infants.

Oxidation of orally administered [13C]glucose and [13C]lactose and fecal recovery of malabsorbed substrates were determined in two groups of premature infants. Eighteen studies were performed with six infants at Johns Hopkins Hospital (JHH); 24 studies were performed with nine infants at Columbus Children's Hospital (CCH). The two groups differed in that JHH infants had shorter gestations but were older when studied. Fecal 13C loss after [13C]glucose administration did not differ between the two groups. Compared with glucose, the metabolism of lactose appeared to involve more malabsorption and colonic fermentation in JHH infants than in CCH infants and resulted in higher fecal losses of substrate carbon. Maturation appeared to involve increased proximal intestinal absorption and greater retention of absorbed carbohydrate. Simultaneous absorption of substrate from the small and large intestine may limit the usefulness of breath tests for 13C in the premature infant.