Angiotropic syringomatous carcinoma

Syringomatous carcinoma (SC) is a slow‐growing malignant skin tumor that usually affects the face or scalp. An 83‐year‐old female developed SC on the sole, a rare location. Histopathologically, numerous ducts with few keratinizing cysts were seen in the upper dermis, and cords, strands and nests with sclerotic stroma were seen in the deep dermis and subcutis. In addition to the perineural and intraneural invasion of the tumor, the tumor cells had also invaded the vessel walls. There was no intravasation of tumor cells or interruption of the endothelium. Because melanoma with vascular wall invasion without intravasation of melanoma cells or interruption of the endothelium has been called angiotropic melanoma, we termed the present tumor angiotropic SC. Tumor cells showed wide local invasion.     

Decreased pituitary-gonadal secretion in men with obstructive sleep apnea

Decreased libido is frequently reported in male patients with obstructive sleep apnea (OSA). The decline in morning serum testosterone levels previously reported in these patients was within the normal adult male range and does not explain the frequent association of OSA and sexual dysfunction. We determined serum LH and testosterone levels every 20 min between 2200-0700 h with simultaneous sleep recordings in 10 men with sleep apnea and in 5 normal men free of any breathing disorder in sleep. The mean levels and area under the curve of LH and testosterone were significantly lower in OSA patients compared with controls [LH, 24.9 +/- 10.2 IU/liter.h vs. 43.4 +/- 9.5 (P < 0.005); testosterone, 67.2 +/- 11.5 nmol/liter.h vs. 113.3 +/- 26.8 (P < 0.003)]. Four of 10 patients had hypogonadal morning (0700 h) serum testosterone levels. Analysis of covariance (ANCOVA) revealed that the 2 groups differed significantly in the amount of LH and testosterone secreted at night independent of age or degree of obesity. After partialing out body mass index, there was a significant negative correlation between the amounts of LH and testosterone secreted at night and the respiratory distress index, but not with degree of hypoxia. Our findings suggest that OSA in men is associated with dysfunction of the pituitary-gonadal axis. The relation between LH-testosterone profiles and the severity of OSA suggests that sleep fragmentation and, to a lesser extent, hypoxia in addition to the degree of obesity and aging may be responsible for the central suppression of testosterone in these patients.     

Nodular duodenitis involving CD8+ cell infiltration in patients with ulcerative colitis

BACKGROUND/AIMS: Limited efforts have been made to determine changes in the upper gastrointestinal tract in ulcerative colitis. The aim of this study was to analyze gastroduodenal lesions in patients with ulcerative colitis. METHODOLOGY: The endoscopical appearance of lesions in the duodenum and stomach was first examined. Biopsy specimens taken from 25 patients with ulcerative colitis, as well as 21 with Crohn's disease and 16 with nonspecific gastroduodenitis who had no Helicobacter pylori infection, were then evaluated by histology and immunohistochemistry for CD8, CD68 and HLA-DR. In ulcerative colitis patients, the HLA-phenotype was also analyzed by the standard NIH complement-dependent microlymphocyte toxicity assay. RESULTS: Endoscopically evident alteration of nodularity in the descending part of duodenum was prominent in ulcerative colitis and Crohn's disease, but not gastroduodenitis. Histological inflammatory change of the duodenal bulb in ulcerative colitis and Crohn's disease was mild as compared to gastroduodenitis cases. Endoscopic and histological change (redness and deformity of villi) in the duodenum were more prominent in ulcerative colitis patients with pancolitis than those with left-sided/proctitis. CD8+ cells infiltrating both the duodenum and stomach were increased in ulcerative colitis and Crohn's disease as compared to gastroduodenitis whereas focal perifoveolar accumulation of CD68+ cells and enhanced epithelial expression of HLA-DR were characteristic of Crohn's disease. Histopathological alteration in the duodenum was particularly prevalent in ulcerative colitis patients with HLA-DR4 and Cw1. CONCLUSIONS: Nodular, histologically mild duodenitis involving CD8+ cell infiltration, the severity of which positively correlates with the extent of colitis, is characteristic of ulcerative colitis.     

Knee joint angle and vasti muscle electromyograms during fatiguing contractions

We compared vasti muscle electromyograms for two knee joint angles during fatiguing tetanic contractions. Tetanic contraction of the knee extensors was evoked for 70 s by electrical stimulation of the femoral nerve at knee joint angles of 60° (extended, with 0° indicating full extension) and 110° (flexed) in eight healthy men. Surface electromyography was recorded from the vastus intermedius (VI), vastus lateralis (VL) and vastus medialis (VM) muscles. Knee extension force and M‐wave amplitudes and durations were calculated every 7 s, which were normalized by the initial value. Normalized knee extension force was decreased at the flexed knee joint angle compared with that of the extended knee joint angle (P<0·05). Decreased normalized M‐wave amplitude and increased normalized M‐wave duration of the VI were greater at the flexed knee joint angle than the extended knee joint angle (P<0·05), whereas those for the VL and VM were similar (P>0·05). These results suggest that peripheral fatigue profiles of the VI might be greater at the flexed than the extended knee joint angles, but that of VL and VM might be similar in the tested range of knee joint angles (i.e. 60°–110°) during continuous tetanic contraction induced by electrical stimulation. Therefore, greater reduction of knee extension force at the flexed knee joint angle than the extended knee joint angle may reflect fatigue development of the VI more than other quadriceps femoris components.     

PET Imaging Analysis of Vitamin B<Subscript>1</Subscript> Kinetics with [<Superscript>11</Superscript>C]Thiamine and its Derivative [<Superscript>11</Superscript>C]Thiamine Tetrahydrofurfuryl Disulfide in Rats

Purpose

Thiamine is an essential component of glucose metabolism and energy production. The disulfide derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), is better absorbed than readily-available water-soluble thiamine salts because it does not require the rate-limiting transport system required for thiamine absorption. However, the detailed pharmacokinetics of thiamine and TTFD under normal and pathological conditions have not yet been clarified. C-11-labeled thiamine and TTFD were recently synthesized by our group. In this study, to clarify the differences in pharmacokinetics and metabolism of these probes, a quantitative PET imaging study and radiometabolite analysis of C-11-labeled thiamine and TTFD were performed in the rat heart.

Procedures

Positron emission tomography (PET) imaging with [¹¹C]thiamine and [¹¹C]TTFD was performed in normal rats to determine the pharmacokinetics of these probes, and the radiometabolites of both probes from the blood and heart tissue were analyzed by thin-layer chromatography.

Results

Accumulation of [¹¹C]TTFD was significantly higher than that of [¹¹C]thiamine in the rat heart. Moreover, as a result of the radiometabolite analysis of heart tissue at 15 min after the injection of [¹¹C]TTFD, thiamine pyrophosphate, which serves as a cofactor for the enzymes involved in glucose metabolism, was found as the major radiometabolite and at a significantly higher level than in the [¹¹C]thiamine-injected group.

Conclusions

PET imaging techniques for visualizing the kinetics and metabolism of thiamine using [¹¹C]thiamine and [¹¹C]TTFD were developed in this study. Consequently, noninvasive PET imaging for the pathophysiology of thiamine-related cardiac function may provide novel information about heart failure and related disorders.

     

Assessment of Low LDL Cholesterol in Patients Treated by PCSK9 Inhibition: Comparison of Martin/Hopkins and Friedewald Estimations

Purpose

Recent guidelines recommend further reduction of low-density lipoprotein cholesterol (LDL-C) in high-risk populations. The use of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) enables many patients to achieve profound reduction in LDL-C. However, in patients with low cholesterol, the commonly used Friedewald equation tends to underestimate LDL-C, which may result in undertreatment. We aimed to compare Friedewald LDL-C estimation with the more novel Martin/Hopkins method in PCSK9i-treated patients achieving low LDL-C.

Methods

We investigated high-risk patients treated by PCSK9i in whom Friedewald LDL-C levels were <?70 mg/dL and triglycerides ≤?300 mg/dL. LDL-C was additionally assessed by the Martin/Hopkins method. The compatibility between estimations was evaluated using methods of concordance and reclassification between LDL-C categories (<?25, 25–40, 40–55, 55–70 mg/dL) and according to triglyceride strata.

Results

Mean age was 65?±?10 years. The correlation coefficient between LDL-C estimations was r?=?0.898. Martin/Hopkins reclassified 269 of the 608 patients (44%) to a higher LDL-C category, with 14% of the patients reaching LDL-C >?70 mg/dL. Of the 390 patients achieving Friedewald LDL-C <?55 mg/dL, 113 (29%) were estimated to have LDL-C ≥?55 mg/dL by the Martin/Hopkins equation. The magnitude of discordance between LDL-C estimates was more pronounced in hypertriglyceridemic patients in whom LDL-C reclassification from <?55 to ≥?55 mg/dL was observed in 48%.

Conclusions

In real-world practice of high-risk patients achieving low LDL-C under PCSK9i, Martin/Hopkins algorithm displayed significant proportion of LDL-C upward discordance compared to the Friedewald equation, particularly observed in patients with elevated triglycerides, identifying patients that may need treatment intensification.

     

Enlargement of Intrathoracic Goiter with Unilateral Phrenic Nerve Paralysis Leading to Cardiopulmonary Arrest

As an intrathoracic goiter expands, it causes airway stenosis and phrenic nerve paralysis, and slight respiratory stimuli can trigger sudden life-threatening hypoventilation. A 78-year-old obese woman with a large intrathoracic goiter was found unconscious with agonal breathing in her room early in the morning. Cardiopulmonary resuscitation restored spontaneous circulation. She underwent surgical removal of the goiter; however, she required long-term mechanical ventilation because of atelectasis due to phrenic nerve paralysis. In patients with large intrathoracic goiters, difficulty breathing on exertion and diaphragm elevation on chest X-ray may be significant findings predicting future respiratory failure.