Development of thyroid hormone dependence for growth in the rat: a study involving transplanted fetal, neonatal, and juvenile tissues

The role of thyroid hormones (TH) in the growth of rat tissue of different ages was investigated in a transplant system. Paws from 14- to 15-day-old fetal rats or pieces of xiphoid cartilage from 18- to 20-day fetuses and 2-, 9-, or 30-day-old rats were transplanted under the kidney capsule of control or thyroidectomized (TX) syngeneic adult female hosts and grown there for 11 days. Paw transplants grew equally well, and tissue differentiation was similar in control and TX hosts. The degree of ossification was measured by a histometric procedure and was found to be equivalent in paws that developed in situ until 4 days postpartum and in paw transplants of equivalent age grown for 11 days on the kidneys of euthyroid or TX hosts. These results show that growth and differentiation of the skeletal and other tissues of the paw are not dependent on TH during the transplant period, which encompassed the equivalent of the late fetal and first few days of neonatal life. Transplanted xiphoid cartilage was used to analyze growth and the development of TH dependence of a differentiated tissue which is relatively uniform in animals of different ages. In control and TX hosts, the growth capacity of transplanted xiphoids declined progressively with increasing donor age. The tissue also showed an age-related increase in dependence on TH for growth. The xiphoid transplants from the fetal rats grew equally well in the euthyroid and hypothyroid hosts, but those from 30-day-old rats showed a near-total dependence on TH for growth. Overall, the results indicate that rat supportive tissues begin to develop a dependence on TH for growth during the second week postpartum.     

[11C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

The PET tracer [¹¹C]5-hydroxytryptophan ([¹¹C]5-HTP), which is converted to [¹¹C]5-hydroxytryptamine ([¹¹C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [¹¹C]5-HTP in rat? Male rats were scanned with [¹¹C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [¹¹C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [¹¹C]5-HTP uptake, and the k₃. This was unexpected as NSD 1015 directly inhibits the enzyme converting [¹¹C]5-HTP to [¹¹C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [¹¹C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.     

Association between a longer duration of illness, age and lower frontal lobe grey matter volume in schizophrenia

The frontal lobe has an extended maturation period and may be vulnerable to the long-term effects of schizophrenia. We tested this hypothesis by studying the relationship between duration of illness (DoI), grey matter (GM) and cerebro-spinal fluid (CSF) volume across the whole brain. Sixty-four patients with schizophrenia and 25 healthy controls underwent structural MRI scanning and neuropsychological assessment. We performed regression analyses in patients to examine the relationship between DoI and GM and CSF volumes across the whole brain, and correlations in controls between age and GM or CSF volume of the regions where GM or CSF volumes were associated with DoI in patients. Correlations were also performed between GM volume in the regions associated with DoI and neuropsychological performance. A longer DoI was associated with lower GM volume in the left dorsomedial prefrontal cortex (PFC), right middle frontal cortex, left fusiform gyrus (FG) and left cerebellum (lobule III). Additionally, age was inversely associated with GM volume in the left dorsomedial PFC in patients, and in the left FG and CSF excess near the left cerebellum in healthy controls. Greater GM volume in the left dorsomedial PFC was associated with better working memory, attention and psychomotor speed in patients. Our findings suggest that the right middle frontal cortex is particularly vulnerable to the long-term effect of schizophrenia illness whereas the dorsomedial PFC, FG and cerebellum are affected by both a long DoI and aging. The effect of illness chronicity on GM volume in the left dorsomedial PFC may be extended to brain structure-neuropsychological function relationships.     

Human autonomic and cerebrovascular responses to inspiratory impedance

BACKGROUND: We evaluated the influence of breathing through an inspiratory Impedance Threshold Device (ITD) on autonomic neural and cerebrovascular function. METHODS: Eight subjects breathed through a sham ITD (0 cmH2O) and an active ITD (-7 cmH2O) in the supine position. We recorded the ECG, finger photoplethysmographic arterial pressure, cerebral blood flow velocity, and muscle sympathetic nerve activity (MSNA). In a randomized, counterbalanced design, subjects breathed spontaneously and also breathed at a set cadence of 15 breaths/min (0.25 Hz) for 3 minutes each. Data were analyzed in both time and frequency domains. RESULTS: Breathing through the active ITD increased mean arterial pressure by approximately 5 mm Hg, heart rate by 2 bpm, and mean cerebral blood flow velocity by 10% (p<0.05) with no effect on MSNA or estimates of vagal-cardiac control (p>0.05). The active ITD did not affect oscillations of interbeat R-R intervals, arterial pressures, or cerebral flow velocities within the low frequency (LF) domain of the power spectrum (p>0.05). Cross spectral analysis revealed no effect of the active ITD on transfer function magnitudes among arterial pressures and R-R intervals, or between arterial pressures and cerebral blood flow velocities at the LF (p>0.05). CONCLUSIONS: Our results demonstrate that the ITD increases arterial pressure, heart rate, and cerebral blood flow velocity independent of changes in autonomic cardiovascular control or dynamic cerebral autoregulation. Use of an active ITD in situations of acute central hypovolemia, such as during hemorrhage, may slow the progression to hemodynamic instability in bleeding patients who retain the ability to ventilate spontaneously and robustly.     

The diagnostic value of fine needle aspiration in parotid lumps

Introduction

Fine needle aspiration (FNA) is a safe and quick method of diagnosing superficial lumps, which aids preoperative planning. However, FNA of the parotid gland has not gained the widespread acceptance noted in other head and neck lumps. The aim of this study was to determine the ability of FNA of the parotid gland to differentiate benign and malignant disease, and to determine the impact on surgical outcome.

Methods

A retrospective analysis of 201 consecutive parotid operations with preoperative FNA in a large district hospital in the UK was performed. The diagnostic characteristics were calculated for benign and malignant disease, and the impact on surgical procedure was determined.

Results

In identifying benign disease, FNA has a sensitivity of 85% and a specificity of 76%. In detecting malignant disease, FNA has a sensitivity and specificity of 52% and 92% respectively. A false positive on FNA was associated with a higher incidence of neck dissection.

Conclusions

FNA is a useful diagnostic test. However, owing to low sensitivity, it is necessary to interpret it in the context of all other clinical information.     

Does Tweeting Improve Citations? One-Year Results From the TSSMN Prospective Randomized Trial

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Adherence to continuous positive airway pressure treatment in patients with Alzheimer's disease and obstructive sleep apnea.

OBJECTIVE: This analysis examined whether patients with Alzheimer disease (AD) tolerate continuous positive airway pressure (CPAP). METHOD: Thirty patients with AD were randomized to CPAP or sham CPAP and completed sleep, depression, and quality-of-life questionnaires. Participants could choose to continue treatment after the trial. RESULTS: Patients wore CPAP for 4.8 hours per night. More depressive symptoms were associated with worse adherence (rS=-0.37; N=30, p<0.04). Patients who continued using CPAP had fewer depressive symptoms (t [19]=2.45, p=0.02) and better adherence (t [19]=2.32, p=0.03) during the trial. CONCLUSION: Patients with AD with obstructive sleep apnea can tolerate CPAP. Adherence and long-term use may be more difficult among those patients with more depressive symptoms.     

Recent Administration of Iodinated Contrast Renders Core Infarct Estimation Inaccurate Using RAPID Software

BACKGROUND AND PURPOSE:Automated CTP software is increasingly used for extended window emergent large-vessel occlusion to quantify core infarct. We aimed to assess whether RAPID software underestimates core infarct in patients with an extended window recently receiving IV iodinated contrast.MATERIALS AND METHODS:We reviewed a prospective, single-center data base of 271 consecutive patients who underwent CTA ± CTP for acute ischemic stroke from May 2018 through January 2019. Patients with emergent large-vessel occlusion confirmed by CTA in the extended window (>6 hours since last known well) and CTP with RAPID postprocessing were included. Two blinded raters independently assessed CT ASPECTS on NCCT performed at the time of CTP. RAPID software used relative cerebral blood flow of <30% as a surrogate for irreversible core infarct. Patients were dichotomized on the basis of receiving recent IV iodinated contrast (<8 hours before CTP) for a separate imaging study.RESULTS:The recent IV contrast and contrast-naïve cohorts comprised 23 and 15 patients, respectively. Multivariate linear regression analysis demonstrated that recent IV contrast administration was independently associated with a decrease in the RAPID core infarct estimate (proportional increase = 0.34; 95% CI, 0.12–0.96; P = .04).CONCLUSIONS:Patients who received IV iodinated contrast in proximity (<8 hours) to CTA/CTP as part of a separate imaging study had a much higher likelihood of core infarct underestimation with RAPID compared with contrast-naïve patients. Over-reliance on RAPID postprocessing for treatment disposition of patients with extended window emergent large-vessel occlusion should be avoided, particularly with recent IV contrast administration.

Quantifying core infarction versus viable ischemic penumbra is at the crux of patient selection for mechanical thrombectomy (MT) in the setting of anterior circulation emergent large-vessel occlusion (ELVO). While patients with large infarcts tend to demonstrate worse clinical outcomes following reperfusion, successful recanalization of sizable ischemic penumbra, indicative of salvageable tissue, may result in drastic clinical improvement.¹ Segregation of core infarction from ischemic penumbra is particularly relevant for extended window ELVOs (>6 hours since last known well [LKW]).^2,3The semiquantitative ASPECTS system is highly predictive of clinical outcome with ELVO but demonstrates high inter- and intrareader variability.^4,5 Additionally, ASPECTS regions are volumetrically weighted unequally; consequently, patients with the same ASPECTS may have different core infarct volumes depending on the regions involved. The automated quantitative RApid processing of PerfusIon and Diffusion (RAPID; iSchemaView) CTP platform offers standardized and numeric estimation of core infarct and ischemic penumbra, lessening reliance on neuroradiologic ASPECTS interpretation. RAPID estimates a variety of perfusion parameters indicative of cerebral hemodynamics at the moment of scanning. Accordingly, RAPID may predict tissue fate in the hyperacute setting (<1 hour since LKW). NCCT, however, is dependent on parenchymal hypoattenuation, which becomes apparent at least several hours from symptom onset.RAPID software has been validated in multiple clinical trials, notably in DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo) and DEFUSE-3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3), both using RAPID for patient selection for MT in extended window ELVOs. Patients allocated to MT versus best medical therapy alone in the DAWN and DEFUSE-3 trials demonstrated markedly better clinical outcomes with unprecedented numbers needed to treat (NNT) of 2.8 and 4, respectively, to achieve functional independence at 90 days.^2,3Through more ubiquitous RAPID use, we encountered a recurrent phenomenon in which transfer patients with extended window ELVO demonstrated MCA territory hypoattenuation on NCCT but with disproportionately small and, in some instances, zero RAPID estimated core infarct. Essentially, all ELVO transfers to our institution are recent recipients of IV iodinated contrast. Given this imaging incongruity and our ongoing need to optimize patient selection for MT, we aimed to assess whether RAPID software underestimated core infarct volume in patients who received recent (<8 hours) IV contrast for a separate imaging study, most commonly CTA ± CTP at an outside hospital before transfer.     

Choosing general surgery: insights into career choices of current medical students

HYPOTHESIS: The number of unfilled general surgery programs in the United States increased from 4 in 1999 to 41 in 2001. This study seeks to determine if changes in student attitudes occurring during their medical school careers and during the third-year general surgery clerkship contribute to a decline in interest in a surgical career. DESIGN: Prospective survey of medical students at a public medical school in California. PARTICIPANTS AND METHODS: Each medical student received a survey via the Internet. Responses were anonymous. Once quantified, chi(2) analysis was used for comparison and analysis of survey results. Comparisons were made between individual class years and on the basis of whether the respondent completed the third-year general surgery clerkship. RESULTS: Of 368 surveys sent, 232 (63%) were successfully completed and included in the study. Comparison of students' attitudes before and after completion of their general surgery clerkship showed that following surgical course exposure more students believed surgery lacked breadth of expertise, limitations over stress, control over one's time, regularity of schedule, adequacy of leisure time, and income commensurate to workload (P<.05). These results are also consistent in comparisons between individual class years. CONCLUSIONS: Data suggest that medical students seem to be more concerned with issues of "controllable lifestyle" such as adequacy of family and/or leisure time, high level of stress, and amount of work and commitment. The erosion of income differential between demanding and less taxing specialties was also an important cause cited for the flagging interest in surgical disciplines.     

Trimethoprim versus gentamicin for the prevention of bacteriuria following transrectal biopsy of the prostate--do patients need additional anaerobic cover?

OBJECTIVES: To study the incidence of aerobic and anaerobic bacteriuria in patients undergoing transrectal ultrasound-guided biopsies of the prostate. A comparative assessment of efficacy of trimethoprim with gentamicin for the prevention of bacteriuria following the transrectal biopsy of the prostate. To assess the need for additional prophylaxis against anaerobes for patients undergoing transrectal biopsies of the prostate gland. PATIENTS AND METHODS: In a pilot study during 1995-1997, all the patients undergoing transrectal ultrasound-guided biopsy of the prostate were randomised to receive either trimethoprim or gentamicin prophylaxis prior to the procedure. Midstream urine (MSU) samples were taken just prior to biopsy and 72 h later. A patient questionnaire to determine the symptoms of urinary tract infection (UTI) accompanied the 72-hour MSU request form. Urine samples were cultured aerobically, using a semiquantitative technique if dipstick analysis revealed the presence of blood, pus cell or nitrite. In addition to the routine aerobic culture, post-biopsy samples were also cultured for anaerobes by direct and enrichment methods. Bacteriuria was defined as a pure or mixed growth of 10(5) colony-forming units/ml. Fisher's test of exact probability was used for statistical analysis. RESULTS: 115 patients were available for final analysis. 53 had received gentamicin and 62 trimethoprim. Four patients had pre-existing bacteriuria (3.5%), 3 in the trimethoprim group and 1 in the gentamicin group. Post-operative bacteriuria developed in 5 patients given gentamicin (9.4%) and 1 given trimethoprim (1.6%). This difference was not statistically significant (p = 0.085). Post-procedure bacteriuria was asymptomatic in all but 1 case. Anaerobes were detected in only 5 MSUs (4.3%) post-biopsy. CONCLUSION: Though there was no statistical significant difference in the rates of bacteriuria following administration of trimethoprim and gentamicin, data appear to favour trimethoprim prophylaxis. Further studies are warranted. Transrectal biopsy of the prostate is associated with a low incidence of anaerobic UTI. In view of the very low incidence of anaerobic bacteriuria, routine antibacterial prophylaxis against anaerobes does not appear to be justified.