Depriving neonatal rats of milk from early lactation has long-term consequences on mammotrope development

The sudden appearance of prolactin-releasing cells during the early postnatal period of the rat is initiated by a small milk-borne peptide. Depriving newborn rats of this early milk factor severely retards mammotrope differentiation during the neonatal period. In the present work, we extend our study of early milk deprivation to the adult. To this end, newborn litters were crossfostered onto mothers that had given birth the same day or one week earlier in order to deprive pups in the latter group of early milk. At 5, 15, and 30 d of age, rats deprived of such milk had decreased percentages of mammotropes (as measured by reverse hemolytic plaque assay, RHPA) when compared to nondeprived animals (P<0.05). By 45 d, the percentage of mammotropes was similar for the two crossfostered groups (P>0.1) and this persisted through d 60. Subsequently, we assessed the secretory capacity of mammotropes from 60-d old rats to secretagogues and found that early milk deprivation had no effect on basal prolactin release (P>0.1), but that it augmented hormone secretion evoked by thyrotropin-releasing hormone (TRH, 100 nM; P<0.01). The inhibitory response to dopamine (DA; 1 μM) and the stimulatory response to angiotensin II (AGII; 100 nM) were not altered by early milk deprivation (P>0.1). Taken together, these results demonstrate that factors in milk from early lactation are required for normal mammotrope differentiation, and that the delay induced by early milk deprivation leads to altered secretory function of mammotropes in adult animals.     

Epinephrine reduces the sedative side effects of epidural sufentanil for labour analgesia

PURPOSE: The use of opioids in labour analgesia has primarily been as an adjuvant to local anesthetics. For early labour, satisfactory analgesia with epidural sufentanil alone is possible. This study evaluates the impact of epinephrine on sedative side effects and analgesia related to the latter technique. METHODS: After Institutional Review Board approval and informed consent this prospective, randomized, double-blind study evaluated 43 nulliparous subjects requesting epidural analgesia. The study site, a tertiary care obstetric unit, accommodates 3500-4500 deliveries annually. Group selection was randomized and blinded by selection of a sealed envelope containing a number which corresponded to a premixed labelled syringe of saline or epinephrine (100 microg/mL). An epidural catheter was placed in a standardized fashion. All subjects received 40 microg of sufentanil and 0.5 mL from the premixed syringe, diluted to 10 mL with NaCl. A blinded observer collected data on maternal sedation, lightheadedness, hemodynamics, oxygenation, and fetal heart rate over a one-hour period following sufentanil injection. RESULTS: The addition of epinephrine significantly (P <0.05) reduced the incidence of sedation and lightheadedness after epidural sufentanil at all data collection points, except two. Analgesic duration was also significantly prolonged by this addition (120 +/- 56 vs 84 +/- 32 min). Maternal satisfaction was high regardless of solution. CONCLUSION: Forty micrograms of epidural sufentanil produces satisfactory analgesia in early labour. The addition of epinephrine improves the side effect profile of this technique while prolonging the duration of analgesia. Epidural sufentanil requires attention to maternal monitoring of oxygenation as maternal desaturation occurred in both groups.     

Clictate: A Computer-Based Documentation Tool for Guideline-Based Care

The use of computer-based documentation tools confers many benefits to the delivery of evidence-based health care. We developed Clictate, a structured reporting environment that utilized standard Windows^TM-based data entry constructs and natural language generation. Clictate has been in use for over 3 years by pediatric providers in an ambulatory setting. More than 50% of our providers use Clictate during the patient encounter. This report describes our results to date, and suggests future opportunities for research and development in the area of computer-based documentation.     

Reactive arthritis of the temporomandibular joints and cervical spine in a child

Background  

Temporomandibular joint (TMJ) arthritis is frequently seen in children with chronic arthritis. It has rarely been described in a non-infectious acute setting. We report a case of reactive arthritis isolated to the TMJs and cervical spine.     

The blast path: theoretical basis, experimental data and clinical application

Use of the "blast path" may be helpful in patients where positioning for ESWL treatments is difficult. Good pressures are maintained along the blast path and an alternate fracture mechanism may be in effect. The rate of fragmentation, assessed using model material, decreases with distance beyond F2.     

Ultrastructure of another spiral organism associated with human gastritis

Summary Campylobacter pylori may not be the only organism that causes active chronic gastritis in man. We report two cases of gastric infection with a spiral organism distinct fromC. pylori. The first patient is a 36-year-old female who presented with epigastric pain and abdominal colic present since childhood and who had 14 cats. Endoscopy was normal. The second patient kept two dogs. Histology of gastric mucosal biopsy specimens in both patients revealed active chronic gastritis, most severe in body mucosa. Giemsa stain revealed bacteria with four to eight spirals, 0.5 m in diameter and 3–7 m in length. The organisms had multiple sheathed flagella at the pole and smooth cell walls without axial filaments. The organisms resembled the gastric spirillum that has been seen in cats, dogs, and nonhuman primates. After antibacterial therapy with bismuth subsalicylate, amoxicillin, and metronidazole, the organisms disappeared in both patients and the gastritis healed.UnlikeC. pylori, this new spirillum prefers to colonize gastric mucosa containing parietal cells. Whereas this type of organism is a common commensal in other mammals, it appears to be associated with and a possible cause of gastritis in humans.     

Biochemical characterisation of para-aminophenol-induced nephrotoxic lesions in the F344 rat

The acute biochemical effects of the nephrotoxin p-aminophenol (PAP) were studied in detail using a combination of conventional bioanalytical and ¹H-NMR spectroscopic methods. Dosing PAP (25–100 mg/kg) to male F344 rats resulted in a dose-related proximal nephropathy with consequent elevations in urinary enzymes, glucose, and urine total protein as shown by conventional methodology. ¹H-NMR spectroscopy at 400 MHz of urine from PAP-treated rats also revealed a characteristic glycosuria, with concomitant amino aciduria. The increased excretion of these compounds indicates functional defects in the proximal tubule and reduced solute reabsorption efficiency. In addition, ¹H-NMR urinalysis and conventional enzymatic analysis showed a dose-related lactic aciduria. Other changes detected by ¹H-NMR included a dose-related reduction in the excretion of citrate (confirmed by a conventional biochemical method) and an increase in the excretion of acetate. The degree of abnormalities shown by ¹H-NMR urinalysis agreed well with histopathological observations and conventional biochemical indices of nephrotoxicity. ¹H-NMR urinalysis therefore serves to highlight changes in the excretion of low MW urine components not routinely studied by conventional biochemical analysis.Abbreviations ALP alkaline phosphatase - APAP paracetamol - BUN blood urea nitrogen - GFR glomerular filtration rate - GOT glutamate oxaloacetate transaminase - LAP leucine aminopeptidase - LDH lactate dehydrogenase - MW molecular weight - NAG N-acetyl--D-glucosaminidase - PAP p-aminophenol - ppm parts per million - TMAO trimethylamine N-oxide - UFR urine flow rate     

Effect of a CCR5 inhibitor on viral loads in macaques dual-infected with R5 and X4 primate immunodeficiency viruses

Human immunodeficiency virus type 1 (HIV-1) fusion with its target cells is initiated by sequential interactions between its envelope glycoprotein, CD4, and a co-receptor, usually CCR5 or CXCR4. Small molecules that bind to CCR5 and prevent its use by R5 HIV-1 strains are now being developed clinically as antiviral drugs. To test whether a block to CCR5 promotes the replication of viruses that enter cells via CXCR4 and are associated with accelerated disease progression, we administered a small molecule CCR5 inhibitor, CMPD 167, to three macaques dual-infected with both R5 (SIVmac251) and X4 (SHIV-89.6P) viruses. CMPD 167 caused a rapid and substantial (on average, 50-fold) suppression of R5 virus replication in each animal. In two of the animals, but not in the third, a rapid, transient, 8- to 15-fold increase in the amount of plasma X4 virus occurred. In neither animal was the increase in X4 viral load sustained throughout therapy, however. These observations may have relevance for the development of CCR5 inhibitors for treatment of HIV-1 infection of humans.