Ultrasound-guided fine-needle aspiration biopsy of solitary pulmonary nodules

Ultrasound-guided fine-needle aspiration biopsy (US-guided FNAB) was performed in 40 patients with solitary pulmonary nodules (SPNs) for evaluation of diagnostic results and complication rates. The final diagnoses of the 40 patients included 30 malignancies and 10 benign lesions. Using US-guided FNAB, the diagnostic yields were 97% (29/30) in malignancies and 60% (6/10) in benign lesions. Of the 29 patients with cytologically proven malignancies, 12 underwent surgical resection. The correlation between cytological results and histologic diagnoses in these 12 was excellent (100%). The size of the nodule did not affect the diagnostic rate or complication rate. Only two patients (5%) developed minimal pneumothorax after US-guided FNAB. We conclude that US-guided FNAB is a useful, safe, and convenient diagnostic tool for SPN, and that malignant pulmonary nodules are more easily diagnosed than benign nodules. © 1995 John Wiley & Sons, Inc.     

Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study

A prospective, double-blind, randomized study of the role of corticosteroids in the treatment of tuberculous pleurisy was performed in 40 patients. All patients received adequate antituberculosis chemotherapy (isoniazid, 300 mg/day; rifampin, 450 mg/day; ethambutol, 20 mg/kg/day) for more than nine months. They were randomly assigned to take prednisolone 0.75 mg/kg/day orally or placebo for the initial treatment, which was tapered gradually for the next two to three months. Twenty-one were treated with steroids and 19 were given a placebo. The two groups were identical with regard to age, sex, duration from onset of symptoms to diagnosis, and initial amount of pleural effusion. The mean duration from symptoms (fever, chest pain, dyspnea) to relief was 2.4 days in the steroid-treated group, and 9.2 days in the placebo group (p less than 0.05). Complete reabsorption of pleural effusion occurred an average of 54.5 days in the steroid-treated group and 123.2 days in the placebo group (p less than 0.01). The development of residual pleural thickening was not influenced by the administration of corticosteroids. No serious side effects were noted during the treatment in either group. We conclude that the administration of corticosteroids, in conjunction with antituberculosis chemotherapy, will resolve the clinical symptoms more quickly and hasten the absorption of pleural effusion in patients with tuberculous pleurisy.     

Inhibitory effects of physalin B and physalin F on various human leukemia cells in vitro.

Physalins B and F were isolated and characterized from the ethanolic extract of the whole plant of Physalis angulata L. (Solanaceae). Both physalin B and physalin F inhibited the growth of several human leukemia cells: K562 (erythroleukemia), APM1840 (acute T lymphoid leukemia), HL-60 (acute promyelocytic leukemia), KG-1 (acute myeloid leukemia), CTV1 (acute monocytic leukemia) and B cell (acute B lymphoid leukemia). Physalin F showed a stronger activity against these leukemia cells than physalin B, especially against acute myeloid leukemia (KG-1) and acute B lymphoid leukemia (B cell). From the structural features, the active site seems to be the functional epoxy group for physalin F and the double bond for physalin B located at carbon 5 and 6; the former is much more active than the latter as regards anti-leukemic effects.     

Immunomodulators from Paris formosana Hayata.

Eight glycosides PF-1 to PF-8 were isolated from the leaves and stems of Paris formosana Hayata (Liliaceae), of which PF-3 (III) was the main compound. It was found that PF-1 to PF-3 (I-III) caused proliferative responses of mouse lymphocytes to concanavalin A and augmentation of mouse granulocyte/macrophage colony forming cells in mouse fibroblast cell L929 conditioned medium. PF-4(IV) and PF-8 showed significant immunomodulatory effects with very low toxicity: they not only caused the same immune responses as PF-1, 2 & 3 but also enhanced the proliferative response of human peripheral whole blood to phytohemagglutinin. PF-5 (V) also increased 3H-thymidine incorporation in ConA-stimulated lymphocytes and in PHA-stimulated human peripheral whole blood, and enhanced the proliferative response of granulocyte/macrophage colony stimulating activity. PF-6(VI) and PF-7(VII) augmented 3H-thymidine incorporation in granulocyte/macrophage colony-forming cells and mitogenic response of PHA-stimulated human peripheral whole blood cells from healthy adults. However, PF-1, 2 and 3 showed hemolytic action, while PF-4 to PF-8 had no hemolytic action at all. On the other hand, the hemolytic action of PF-3 derivatives was reduced as compared with PF-3 but their immune responses did not equal those of PF-3, only showing granulocyte/macrophage colony stimulating activity.     

Alteration in myelin-associated proteins following spinal cord irradiation in guinea pigs.

The aim of this study was to investigate the pathological and cellular basis for radiation-induced myelopathy in guinea pigs by monitoring biochemical alterations in levels of myelin basic protein and 2',3'-cyclic nucleotide phosphohydrolase. Guinea pigs were irradiated to the lumbar region with various doses of neutrons or cobalt gamma irradiation. The ED50s for paralysis were 17.2 Gy and 67.5 Gy for neutron and cobalt irradiation, respectively, and was histologically associated with demyelination. In spinal cords taken from animals at the onset of paralysis myelin basic protein levels were decreased in direct relationship to the radiation dose. The lowest doses to cause paralysis led to a 25% decrease in MBP levels. In a separate experiment, alterations in MBP were measured in the spinal cords over the time period leading up to paralysis. Surprisingly, decreases in MBP were found immediately after the end of the 4 week irradiation period. These early changes in MBP were not markedly dose dependent and occurred with nonparalyzing doses. Dose-dependent decreases were found only just before the onset of paralysis. CNPase activity measured in the same specimens showed changes that were essentially similar to those for MBP. In the CSF, MBP levels were essentially constant until onset of paralysis. This study showed that demyelination, as assessed by the levels of the myelin-associated proteins MBP and CNPase, can occur soon after spinal cord irradiation but that profound dose-dependent changes are seen only immediately preceding the onset of paralysis. Although increases in MBP in the CSF were associated with the onset of radiation-induced myelopathy, its assay is unlikely to predict this complication of irradiation.     

Long-term corticosteroid effect on lymphocyte and polymorphonuclear cell function in asthmatics

The effect of long-term alternate-day steroid administration on lymphocyte and polymorphonuclear cell (PMN) functions was studied in 10 steroid-dependent adult asthmatic patients. The duration of alternate-day prednisone usage ranged from 3 to 12 yr with an average of 6.7 ± 3.6 yr. Maintenance steroid dosage at the time of study ranged from 20 to 50 mg on alternate days, averaging 31 ± 8 mg. Prednisone caused marked lymphopenia, suppression of phytohemagglutin (PHA) lymphocyte transformation and PMN adherence 4 hr after ingestion. By 24 hr these measurements returned to normal or higher. These effects appeared at all doses between 20 and 50 mg of prednisone. In contrast, there was no statistically significant suppression of the total leukocyte count, total and active erythrocyte (E) rosette-forming lymphocytes, serum immunoglobulin concentrations, polymorphonuclear cell (PMN) phagocytosis, or delayed skin reactivity. We conclude that the acute effects of prednisone on lymphocyte and PMN function are transient and return to normal levels by 24 hr. The continued administration of beclomethasone dipropionate by inhalation did not interfere with the recovery of the transient leukocyte abnormalities induced by oral prednisone.     

Effect of inhibitors of transmethylation on histamine release from human basophils

Methylation reactions mediated by $\text{S-}\text{adenosyl-}\text{l}\text{-methionine}$ (AdoMet) play an important role in a number of biological reactions including bacterial and human monocyte chemotaxis. This study evaluated the role of methylation reactions in histamine release from human basophils. Methylation was blocked by several methods. Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), an inhibitor of adenosine deaminase (EC 3.5.4.4), blocked the IgE-mediated histamine release with an ic₅₀ (concentration of drug required to produce 50 per cent inhibition) of 0.33 mM. Preincubation of leukocytes with adenosine caused some inhibition of IgE-mediated histamine release. This inhibition by adenosine was potentiated by the addition of 1 × 10^?5 M EHNA which alone did not affect histamine release. Further addition of l-homocysteine thiolactone at 1 × 10^?4 M potentiated the inhibitory effect of EHNA plus adenosine. The effect of l-homocysteine thiolactone was dose dependent. 3-Deazaadenosine (DZA), an inhibitor of $\text{S-}\text{adenosyl-}\text{l}\text{-homocysteine}$ hydrolase (EC 3.3.1.1) inhibited IgE-initiated histamine release from human basophils with an ic₅₀ of ~1 mM. This inhibition was potentiated by l-homocycsteine thiolactone. The inhibition by DZA was not potentiated by two different phospho-diesterase inhibitors suggesting that the action of DZA was not through changes in intracellular levels of cyclic AMP. DZA inhibited during the Ca²⁺-independent activation step of IgE-mediated basophil histamine release. In contrast, when histamine release was induced by the calcium ionophore A23187, f'Met-Leu-Phe or zymosan-activated serum, there was either no inhibition or enhancement of histamine release by these inhibitors of transmethylation. These results suggest that AdoMet-mediated methylation plays an important role in IgE-initiated histamine secretion from human basophils and that release induced by A23187, fMet-Leu-Phe, or C5A, bypasses this reaction step.     

A histochemical study on the development of hydroxysteroid dehydrogenases in tadpole ovaries.

Indifferent gonads and ovaries of Rana catesbeiana tadpoles at various developmental stages were investigated histochemically for the development of activities of Δ⁵-3β- and 17β-hydroxysteroid dehydrogenases (HSDs). It was found that activities of the two enzymes occurred simultaneously; that of 17β-HSD was usually weaker by visualization. They began to appear weakly in the indifferent gonad. The activities became stronger as the ovaries differentiated until the enzymes heavily occupied the cytoplasm of small auxocytes. While the auxocytes were growing in size, the activities of the two HSDs were decreasing and eventually became confined to a few patches in large auxocytes of metamorphosing tadpoles. Enzyme activities also occurred in follicle cells. They developed to a considerable extent in newly metamorphosed froglets. The present study presents histochemical evidence for developmental changes in the distribution of these two enzymes. The results also indicate capability of steroid hormone metabolism in the tadpole ovary during the course of sex differentiation. The localization of ooplasmic and follicular activities of the HSDs and the pattern of their development in differentiating ovaries are reported for the first time in amphibians.     

Sonothrombolysis in ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

BackgroundPreclinical studies have demonstrated that high mechanical index (MI) impulses from a diagnostic ultrasound transducer during an intravenous microbubble infusion (sonothrombolysis) can restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI).ObjectivesThis study tested the clinical effectiveness of sonothrombolysis in patients with STEMI.MethodsPatients with their first STEMI were prospectively randomized to either diagnostic ultrasound–guided high MI impulses during an intravenous Definity (Lantheus Medical Imaging, North Billerica, Massachusetts) infusion before, and following, emergent percutaneous coronary intervention (PCI), or to a control group that received PCI only (n = 50 in each group). A reference first STEMI group (n = 203) who arrived outside the randomization window was also analyzed. Angiographic recanalization before PCI, ST-segment resolution, infarct size by magnetic resonance imaging, and systolic function (LVEF) at 6 months were compared.ResultsST-segment resolution occurred in 16 (32%) high MI PCI versus 2 (4%) PCI-only patients before PCI, and angiographic recanalization was 48% in high MI/PCI versus 20% in PCI only and 21% in the reference group (p < 0.001). Infarct size was reduced (29 ± 22 g high MI/PCI vs. 40 ± 20 g PCI only; p = 0.026). LVEF was not different between groups before treatment (44 ± 11% vs. 43 ± 10%), but increased immediately after PCI in the high MI/PCI group (p = 0.03), and remained higher at 6 months (p = 0.015). Need for implantable defibrillator (LVEF ≤30%) was reduced in the high MI/PCI group (5% vs. 18% PCI only; p = 0.045).ConclusionsSonothrombolysis added to PCI improves recanalization rates and reduces infarct size, resulting in sustained improvements in systolic function after STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330).     

A Multicentre Evaluation of the Role of the Prostate Health Index (PHI) in Regions with Differing Prevalence of Prostate Cancer: Adjustment of PHI Reference Ranges is Needed for European and Asian Settings

Asians have a lower incidence of prostate cancer (PC). We compared the performance of the Prostate Health Index (PHI) for 2488 men in different ethnic groups (1688 Asian and 800 European men from 9 sites) with PSA 2–20 ng/ml and PHI test and transrectal ultrasound-guided biopsy results available. Of these, 1652 men had PSA 2–10 ng/ml and a normal digital rectal examination and underwent initial biopsy. The proportions of PC (Gleason ≥6) and higher-grade PC (HGPC, Gleason ≥7) across different PHI ranges were compared. The performance of PSA and PHI was compared using the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA). Among Asian men, HGPC would be diagnosed in 1.0%, 1.9%, 13%, and 30% of men using PHI thresholds of <25, 25–35, 35–55, and >55, respectively. At 90% sensitivity for HGPC (PHI >30), 56% of biopsies and 33% of Gleason 6 PC diagnoses could have been avoided. Among European men, HGPC would be diagnosed in 4.1%, 4.3%, 30%, and 34% of men using PHI thresholds of <25, 25–35, 35–55, and >55, respectively. At 90% sensitivity for HGPC (PHI >40), 40% of biopsies and 31% of Gleason 6 PC diagnoses could have been avoided. AUC and DCA confirmed the benefit of PHI over PSA. The benefit of PHI was also seen at repeat biopsy (n = 397) and for PSA 10–20 ng/ml (n = 439). PHI is effective in cancer risk stratification for both European and Asian men. However, population-specific PHI reference ranges should be used.