Michael W. Yeh

False-Negative Fine-Needle Aspiration Cytology Results Delay Treatment and Adversely Affect Outcome in Patients with Thyroid Carcinoma

Clinicians have become reliant on fine-needle aspiration (FNA) cytology in the diagnosis of thyroid nodules. We encountered several patients who had thyroid cancer at operation despite having had FNAs that never showed malignant or suspicious cells. Hence, we retrospectively studied 100 consecutive patients with histologically proven thyroid cancer who had undergone preoperative FNA. Fourteen of these patients had cancers that were not detected by FNA, three of whom developed widespread disease. The sensitivity of FNA was 79%, the false-negative rate 21%, and the inadequate rate 12%. FNA was less sensitive in detecting follicular and Hürthle cell carcinomas compared to papillary carcinomas. FNAs interpreted by cytopathologists at a major university center were more sensitive than those performed elsewhere. A single false-negative FNA delayed surgical treatment by 28 months, sometimes despite clinical evidence suggesting malignancy. Subjects whose tumors were not detected by FNA experienced delayed treatment, had higher rates of vascular and capsular invasion, and were more likely to have persistent disease at follow up (hazard ratio 2.28). False-negative results remain a concern in the cytologic diagnosis of thyroid cancer. Although FNA is a useful test, clinical findings should overrule cytologic data in order for timely treatment to occur.

Fever Response in Elderly Nursing Home Residents: Are the Older Truly Colder?

Objective To test the hypothesis that many nursing home residents with an apparently blunted fever response (maximum temperature <101°F) may actually have a significant change in temperature (ΔT ≥ 2.4°F) which is not recognized because of a low baseline temperature.

Cytokine-Stimulated, But Not HIV-Infected, Human Monocyte-Derived Macrophages Produce Neurotoxic Levels of l-Cysteine

Approximately one-quarter of individuals with AIDS develop neuropathological symptoms that are attributable to infection of the brain with HIV. The cognitive manifestations have been termed HIV-associated dementia. The mechanisms underlying HIV-associated neuronal injury are incompletely understood, but various studies have confirmed the release of neurotoxins by macrophages/microglia infected with HIV-1 or stimulated by viral proteins, including the envelope glycoprotein gp120. In the present study, we investigated the possibility that l-cysteine, a neurotoxin acting at the N-methyl-d-aspartate subtype of glutamate receptor, could contribute to HIV-associated neuronal injury. Picomolar concentrations of gp120 were found to stimulate cysteine release from human monocyte-derived macrophages (hMDM) in amounts sufficient to injure cultured rat cerebrocortical neurons. TNF-α and IL-1β, known to be increased in HIV-encephalitic brains, as well as a cellular product of cytokine stimulation, ceramide, were also shown to induce release of cysteine from hMDM in a dose-dependent manner. A TNF-α-neutralizing Ab and an IL-1βR antagonist partially blocked gp120-induced cysteine release, suggesting that these cytokines may mediate the actions of gp120. Interestingly, hMDM infected with HIV-1 produced significantly less cysteine than uninfected cells following stimulation with TNF-α. Our findings imply that cysteine may play a role in the pathogenesis of neuronal injury in HIV-associated dementia due to its release from immune-activated macrophages but not virus-infected macrophages. Such uninfected cells comprise the vast majority of mononuclear phagocytes (macrophages and microglia) found in HIV-encephalitic brains.

Failure of beta-amyloid protein fragment 25–35 to cause hippocampal damage in the rat

Considerable excitement has been generated as of late over reports that fragments of the amyloid precursor protein can be neurotoxic both in vivo and in vitro. In this brief report we study the neurotoxicity of the fragment corresponding to amino acids 25-35 of the beta-amyloid protein in the hippocampus in vivo. Under the conditions studied, we do not observe any evidence of consistent, dose-related damage above that seen with vehicle alone.

PARATHYROID HORMONE ASSAY PREDICTS HYPOCALCAEMIA AFTER TOTAL THYROIDECTOMY

Background:u2003 Postoperative parathyroid gland function after total thyroidectomy (TT) has traditionally been monitored by the measurement of serum calcium concentrations. The purpose of this study is to determine whether measurement of parathyroid hormone (PTH) concentrations in the early postoperative period accurately predicts patients at risk of developing hypocalcaemia.

Update on current models of HIV-related neuronal injury: platelet-activating factor, arachidonic acid and nitric oxide

This review aims to summarize recent work related to the pathogenesis and possible treatment of neuronal injury in the acquired immunodeficiency syndrome (AIDS), especially with reference to potential neurotoxic substances released by HIV-infected or gp120-stimulated macrophages/microglia. Approximately a third of adults and half of children with AIDS eventually suffer from neurological manifestations, including dysfunction of cognition, movement, and sensation. Among the various pathologies reported in brains of patients with AIDS is neuronal injury and loss. A paradox arises, however, because neurons themselves are for all intents and purposes not infected by human immunodeficiency virus type 1 (HIV-1). This paper reviews recent evidence suggesting that at least part of the neuronal injury observed in the brains of AIDS patients is related to excessive influx of Ca2+ after the release of potentially noxious substances from HIV-infected or gp120-stimulated macrophages/microglia. There is growing support for the existence of HIV- or immune-related toxins that lead indirectly to the injury or demise of neurons via a potentially complex web of interactions between macrophages (or microglia), astrocytes, and neurons. HIV-infected monocytoid cells (macrophages, microglia or monocytes), especially after interacting with astrocytes, secrete substances that potentially contribute to neurotoxicity. Not all of these substances are yet known, but they may include eicosanoids, i.e. arachidonic acid and its metabolites, as well as platelet-activating factor. Other candidate toxins include nitric oxide (NO.), superoxide anion (O2.-), and the N-methyl-D-aspartate (NMDA) agonist, cysteine. Similarly, macrophages activated by HIV-1 envelope protein gp120 also appear to release arachidonic acid and its metabolites, and cysteine.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of the ligaSure vessel sealing system in laparoscopic adrenalectomy.

Laparoscopic adrenalectomy is the operation of choice for benign adrenal lesions. During laparoscopic surgery, vessels are usually ligated with diathermy, ligaclips, staplers or ultrasonic coagulators. Use of the electrothermal bipolar vessel sealer (LigaSure; Valleylab, Boulder, CO, USA) has recently been described in a variety of procedures, not including adrenalectomy. This article is a retrospective study of 28 patients undergoing laparoscopic adrenalectomy within the University of Sydney Endocrine Surgical Unit at the Royal North Shore Hospital using the LigaSure vessel sealing system. Between July 2004 and August 2005, 28 consecutive patients underwent laparoscopic adrenalectomy using the LigaSure vessel sealing system to divide feeding adrenal vessels as well as the adrenal vein. There were no bleeding complications. The LigaSure vessel sealing system can be safely used to secure haemostasis, including division of the adrenal vein, in laparoscopic adrenalectomy.

TWO HUNDRED CONSECUTIVE PARATHYROID ULTRASOUND STUDIES BY A SINGLE CLINICIAN: THE IMPACT OF EXPERIENCE

OBJECTIVEnTo assess the ability of ultrasound studies, performed by an experienced clinician, to predict surgical findings and provide precise anatomic localization of abnormal parathyroid glands.nnnMETHODSnWe retrospectively examined 200 consecutive parathyroid ultrasound studies performed by a single experienced clinician in our unit. All patients subsequently underwent parathyroidectomy, with histopathologic confirmation of abnormal parathyroid tissue. The correlation between the ultrasound and surgical findings was assessed.nnnRESULTSnOf the 200 study patients, 197 (98.5%) were cured of their disease at the initial operation. Ultrasound studies correctly predicted the surgical findings in 88% of patients, including 168 of 180 (93%) with single gland disease and 7 of 20 (35%) with multiple gland disease (MGD). In all cases in which a single adenoma was identified, precise information regarding its location relative to adjacent anatomic structures was provided. In 92% of these cases, anatomic details correlated closely with surgical findings. Ectopic and descended superior adenomas were most frequently missed. Patients with two nonlocalizing studies (scintigraphy and ultrasonography) had a >50% likelihood of having MGD.nnnCONCLUSIONnIn experienced hands, parathyroid ultrasonography is a highly sensitive technique that provides both localization of enlarged parathyroid glands and precise anatomic detail. Thus, in this study, focused parathyroidectomy was possible in 76.5% of patients. MGD remains difficult to diagnose preoperatively. Nonlocalizing studies should alert the surgeon to a high probability of MGD and prompt the performance of 4-gland exploration.

Mechanism of the impaired T-cell proliferation in adult rats exposed to alcohol in utero

Although attempts have been made to assess the effect of ethanol on the immune responses in individuals with fetal alcohol syndrome, there is no consensus as to the effect of ethanol on the immune system. Evidence that fetal alcohol-exposed (FAE) humans and animals have diminished proliferative response of T-cells to mitogenic lectins is well established. However, little is known about the mechanism of a toxic effect of ethanol on T-cell growth. Thus, a rat model was used to delineate the mode of ethanol action on T-cell proliferation. We found that the diminished T-cell proliferation in young adult FAE rats was due to a decreased responsiveness to interleukin 2 (IL2), but not to an impaired production of IL2 and expression of IL2 receptors (IL2R). Furthermore, the decreased proliferative response did not result from the presence of an excessive suppressor T-cell activity. Measurements of [Ca+2]i and T-cell proliferation were concurrently performed in batches of cells from the same animals. It was demonstrated that an increase in [Ca+2]i induced by Concanavalin A (Con A) in T-cells from FAE rats was not impaired, although the T-cell proliferation induced by Con A was significantly diminished. The results of the IL2-binding study showed that the Kd values and the number of both high- and low-affinity IL2R binding sites on the T-cells of FAE rats were comparable to those of pair-, or chow-fed rats. Finally, the results of the kinetics and rate of the internalization of IL2 showed that (1) the amount of the internalized IL2 was significantly reduced in T-cells from FAE rats, and (2) the half-time (t1/2) for dissociation of IL2 from the receptors in the T-cells from FAE rats was also greater than that of the control rats. These results taken together indicate that ethanol suppresses T-cell proliferation by interfering with events following the IL2-IL2R interaction.

A randomized controlled trial of minimally invasive thyroidectomy using the lateral direct approach versus conventional hemithyroidectomy

BACKGROUNDnThe role of minimally invasive thyroid surgery (MITS) is currently in evolution. The aim of this study is to compare the outcomes of MITS using the direct approach through a lateral incision with conventional hemithyroidectomy (CHT) for the management of atypical thyroid nodules.nnnMETHODSnA prospective, single-blinded, randomized controlled trial involving patients presenting with atypical thyroid nodules of 3-cm diameter or less was performed. Patients were randomized to MITS through a lateral 2.5-cm incision or CHT through a traditional 5- to 6-cm cervicotomy. Pain was measured using a 7-point visual analog scale on the 1st and 10th postoperative days. Serum C-reactive protein was measured on postoperative days 1 and 10. Satisfaction with cosmetic outcome was measured at 3 months.nnnRESULTSnOne-hundred patients were randomized to undergo MITS or CHT. The 2 groups were equivalent in terms of age and thyroid nodule size. Mean operative times were longer for the MITS group (56 vs 46 min, P < .001). Mean pain scores were less in the MITS group on the 1st postoperative day (2.67 vs 3.43, P = .032). Pain scores at 10 days were equivalent (1.5 vs 1.8, P = .36). Serum C-reactive protein levels were equivalent postoperatively. At 3 months, patients undergoing MITS reported a greater mean cosmetic satisfaction score (6.3 vs 5.0, P = .002). Incision lengths measured at 3 months were 2.6 cm for MITS and 5.4 cm for CHT group, P < .001.nnnCONCLUSIONnIn the management of small, atypical thyroid nodules, MITS through a direct lateral approach results in less early postoperative pain and superior cosmetic results when compared with conventional thyroidectomy.