The Hunga Tonga-Hunga Ha'apai Hydration of the Stratosphere.

Following the 15 January 2022 Hunga Tonga-Hunga Ha'apai eruption, several trace gases measured by the Aura Microwave Limb Sounder (MLS) displayed anomalous stratospheric values. Trajectories and radiance simulations confirm that the H2O, SO2, and HCl enhancements were injected by the eruption. In comparison with those from previous eruptions, the SO2 and HCl mass injections were unexceptional, although they reached higher altitudes. In contrast, the H2O injection was unprecedented in both magnitude (far exceeding any previous values in the 17-year MLS record) and altitude (penetrating into the mesosphere). We estimate the mass of H2O injected into the stratosphere to be 146 ± 5 Tg, or ∼10% of the stratospheric burden. It may take several years for the H2O plume to dissipate. This eruption could impact climate not through surface cooling due to sulfate aerosols, but rather through surface warming due to the radiative forcing from the excess stratospheric H2O.

Extreme Outliers in Lower Stratospheric Water Vapor Over North America Observed by MLS: Relation to Overshooting Convection Diagnosed From Colocated Aqua-MODIS Data.

Convectively injected water vapor (H2O) in the North American (NA) summer lowermost stratosphere results in significant outliers in the 100-hPa H2O measurements from the Aura Microwave Limb Sounder (MLS). MLS statistics from 15 years confirm that the NA region contains over 60% of global 100-hPa H2O > 12 ppmv, despite having only ∼1.8% of all MLS observations. A profile sampled in August 2019 stands out, with H 2 O = 26 . 3 ppmv, far exceeding the prior record and the median ∼4.5-ppmv abundance in NA. This particular outlier is associated with a large overshooting convective event (OCE) that spanned multiple U.S. states and persisted for several hours. Colocation of the MLS data over NA with cloud observations from Aqua's Moderate Resolution Imaging Spectroradiometer (MODIS) reveals the unique character of this case, as only 2.3% of MLS profiles are as close to an OCE and only 0.024% of OCEs cover as large an area within a 500-km perimeter of a profile.

Keratinocyte collagenase-1 expression requires an epidermal growth factor receptor autocrine mechanism.

In response to cutaneous injury, expression of collagenase-1 is induced in keratinocytes via alpha2beta1 contact with native type I collagen, and enzyme activity is essential for cell migration over this substratum. However, the cellular mechanism(s) mediating integrin signaling remain poorly understood. We demonstrate here that treatment of keratinocytes cultured on type I collagen with epidermal growth factor receptor (EGFR) blocking antibodies or a specific receptor antagonist inhibited cell migration across type I collagen and the matrix-directed stimulation of collagenase-1 production. Additionally, stimulation of collagenase-1 expression by hepatocyte growth factor, transforming growth factor-beta1, and interferon-gamma was blocked by EGFR inhibitors, suggesting a required EGFR autocrine signaling step for enzyme expression. Collagenase-1 mRNA was not detectable in keratinocytes isolated immediately from normal skin, but increased progressively following 2 h of contact with collagen. In contrast, EGFR mRNA was expressed at high steady-state levels in keratinocytes isolated immediately from intact skin but was absent following 2 h cell contact with collagen, suggesting down-regulation following receptor activation. Indeed, tyrosine phosphorylation of the EGFR was evident as early as 10 min following cell contact with collagen. Treatment of keratinocytes cultured on collagen with EGFR antagonist or heparin-binding (HB)-EGF neutralizing antibodies dramatically inhibited the sustained expression (6-24 h) of collagenase-1 mRNA, whereas initial induction by collagen alone (2 h) was unaffected. Finally, expression of collagenase-1 in ex vivo wounded skin and re-epithelialization of partial thickness porcine burn wounds was blocked following treatment with EGFR inhibitors. These results demonstrate that keratinocyte contact with type I collagen is sufficient to induce collagenase-1 expression, whereas sustained enzyme production requires autocrine EGFR activation by HB-EGF as an obligatory intermediate step, thereby maintaining collagenase-1-dependent migration during the re-epithelialization of epidermal wounds.

Prolonged QT interval and cocaine use.

Cardiovascular consequences of cocaine use are well known, and surveillance for them is common practice in the routine care of cocaine abusers. However, the cardiac electrical abnormalities that arise, although studied in animal experiments, lack correlation with human reports. The case of a 17-year-old girl, who was admitted after a cocaine binge is reported. She was cardiologically asymptomatic, but an admission electrocardiogram was abnormal, with QT interval prolongation. This returned to normal within 24 hours of observation. The literature on the electrophysiologic effects of cocaine on the heart is reviewed.

Atrioventricular asystole as a manifestation of hiccups.

Sinus pause with atrioventricular asystole can be caused by an excessive vagal response. This case report describes a patient in whom this phenomenon developed after hiccups.

Effects of vasoactive drugs on flows through left internal mammary artery and saphenous vein grafts in man.

Vasoactive agents are commonly used in the postcardiopulmonary bypass period to elevate the mean arterial pressure of myocardial revascularization patients. Concern exists that administration of vasoactive agents in this setting may affect flow through saphenous vein and internal mammary artery grafts. Twenty-eight patients were randomly assigned to receive one of the six two-drug combinations of phenylephrine, norepinephrine, and epinephrine. After termination of cardiopulmonary bypass baseline, hemodynamic measurements and electromagnetic flow probe measurements of saphenous vein and internal mammary artery graft flow were made. The first agent was then infused to elevate mean arterial pressure 20 mm Hg. After 5 minutes of stability, hemodynamic and graft flow measurements were repeated. The infusion was terminated, 5 minutes of stability were obtained, and baseline measurements were repeated. The second agent was then infused, and measurements were repeated after a 5-minute stabilization period. Phenylephrine induced a nonsignificant increase in saphenous vein graft flow (68 +/- 31 versus 81 +/- 49 ml/min) and a significant decrease in internal mammary artery graft flow (40 +/- 16 versus 32 +/- 12 ml/min). Norepinephrine induced a significant increase in saphenous vein graft flow (80 +/- 39 versus 97 +/- 39 ml/min) and no significant change in internal mammary artery graft flow (44 +/- 20 versus 45 +/- 20 ml/min). Epinephrine induced a significant increase in both saphenous vein (82 +/- 38 versus 96 +/- 40 ml/min) and internal mammary artery (38 +/- 12 versus 55 +/- 24 ml/min) graft flows. We conclude that administration of vasoactive agents in the postcardiopulmonary bypass period may significantly affect saphenous vein and internal mammary artery graft flows.

Benefit of the perfusion catheter for emergency coronary artery grafting after failed percutaneous transluminal coronary angioplasty.

Of 2,102 consecutive patients who underwent percutaneous transluminal coronary angioplasty, 31 (1.5%) had emergency coronary bypass grafting for failed angioplasty. To determine the potential impact of different therapeutic strategies for controlling associated myocardial ischemia, 3 groups were analyzed. Group 1 comprised 11 patients (36%) in whom a "bailout" catheter was used to maintain anterograde coronary perfusion, group 2 included 16 patients (52%) in whom only intraaortic balloon counterpulsation was used and group 3 contained 4 patients (13%) in whom neither bailout catheter nor intraaortic balloon was used. Despite a longer average time to cardiopulmonary bypass, patients managed with the bailout catheter had a significantly lower incidence of Q-wave myocardial infarctions (9 vs 75%, p less than 0.05) compared with patients managed with intraaortic balloon counterpulsation alone. Those managed with the bailout catheter also had more consistent resolution of ST elevation and greater use of internal mammary artery grafts than patients supported by intraaortic balloon counterpulsation alone.

Prevalence and significance of atrial fibrillation in coronary artery disease (CASS Registry).

Estimates of the prevalence of atrial fibrillation (AF) in patients with coronary artery disease have varied from "frequent" to less than 2%. Data on 18,343 patients with angiographically demonstrated CAD in the Coronary Artery Surgery Study (CASS) registry were reviewed and AF was found to be present in 116 (0.6%) patients. The presence of AF was positively associated with the following clinical and angiographic variables: older age, sex (male), mitral regurgitation and functional impairment due to congestive heart failure. The number of diseased coronary arteries was negatively related to the presence of AF. Atrial fibrillation was an independent predictor of survival and its presence doubled the estimated risk over those patients without AF.

Papillary thyroid cancer in identical twins.

The cases of a set of 19-year old monozygotic twins are presented--the first report of thyroid cancer of follicular origin occurring in identical twins. This report includes a brief review of reports of cancer of various sites in twins. Several studies and reports emphasize genetic factors influencing the concurrence of cancer. Other reports downgrade the likelihood of genetic influence in cancer.

Left main coronary artery stenosis following mediastinal irradiation.

The association of mediastinal radiation therapy and coronary artery disease has been documented over the past three decades. This report describes a case of left main coronary artery stenosis eight years after radiation therapy in a 27-year-old woman. The patient was a young woman with no risk factors for coronary artery disease who had development of new-onset angina at rest. At coronary arteriography, the patient was found to have a tight ostial left main stenosis. The association of mediastinal radiation therapy with fixed and vasospastic coronary artery disease is reviewed. With many patients treated by radiation therapy now surviving their thoracic malignancies, an enlarging young population may be susceptible to the early development of ischemic heart disease.

Meckel's diverticulum: pitfalls in scintigraphic detection in the adult.

The diagnosis of a bleeding Meckel's diverticulum containing ectopic gastric mucosa by 99m-Tc pertechnetate imaging is reported to have a diagnostic accuracy of 90% for patients in the pediatric age group. The usefulness of Meckel's scanning in adults is, however, less certain. We present two patients who illustrate some of the difficulties inherent in Meckel's scanning in adults; one had a false-negative scan despite the presence of ectopic gastric mucosa and the other had a false-positive scan, both confirmed by laparotomy. The available literature indicates that false-positive and false-negative scans occur relatively frequently in adults, but no comprehensive review on this subject exists. Based on our findings, it is suggested that Meckel's scanning be supplemented with small bowel infusion or arteriography or both to improve preoperative diagnosis in adult patients in whom a diverticulum is suspected.

Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis.

101 patients with Clostridium-difficile-associated diarrhoea or colitis were prospectively randomised to 10-day oral courses of metronidazole, 250 mg four times a day, or vancomycin, 500 mg four times a day. 7 did not complete the protocol and were dropped from analysis. Pseudomembranous colitis (PMC) was diagnosed after endoscopy in 33 patients. Of the remaining patients without PMC, 38 had both C difficile culture and cytotoxin and 23 had only culture evidence of C difficile. 52 evaluable patients received vancomycin and 42 received metronidazole. There were two treatment failures with metronidazole and none with vancomycin (p = 0.20); and two relapses with metronidazole versus six with vancomycin (p = 0.17). Treatment in 1 patient in each group was discontinued because of drug intolerance. Response and relapse rates of the 33 patients with PMC were no different from those of the remaining patients. Pharmacy cost for the dosage used was $387.48 to $520.00 for vancomycin and $11.84 for metronidazole. Metronidazole and vancomycin have equivalent efficacy and relapse rates and are tolerated to a similar extent by patients with C-difficile-related diarrhoea and colitis, but metronidazole is considerably more economical.

Urinary concentrating defect of adrenal insufficiency. Permissive role of adrenal steroids on the hydroosmotic response across the rabbit cortical collecting tubule.

Mineralo- and glucocorticoid-deficient states, such as Addison's disease, are partly characterized by an inability to generate a maximally concentrated urine. The purpose of the present study was to develop a model of adrenal insufficiency and to determine whether changes in the intrinsic function of the collecting duct could partly account for this concentrating defect. Two kinds of experiments were performed: an assessment of the in vivo ability of adrenal-ectomized rabbits to concentrate their urine, and an examination of the intrinsic hydroosmotic responsiveness of in vitro perfused collecting ducts isolated from normal and adrenalectomized rabbits. The present study demonstrates that adrenalectomized rabbits are unable to concentrate their urine maximally, and that the in vivo administration of either deoxycorticosterone, 250 mug/kg, or dexamethasone, 50 mug/kg, restored to or toward normal their concentrating ability. When cortical collecting tubules from adrenalectomized rabbits were perfused in vitro, they demonstrated a markedly blunted hydroosmotic response to antidiuretic hormone (ADH), which was corrected by the in vitro addition of either aldosterone (50 pM) or dexamethasone (50 pM), but not progesterone (50 pM). The steroids by themselves, in the absence of ADH, had no intrinsic effect on the water permeability of the collecting duct. The blunted hydroosmotic response across cortical collecting tubules from adrenal-ectomized rabbits was corrected by the addition of either 8-bromo cyclic AMP or a potent phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine. The present studies show that the cortical collecting tubules obtained from adrenalectomized rabbits do not respond normally to ADH. The poor hydroosmotic response to ADH was corrected by exogenous aldosterone, dexamethasone, an analog of cyclic AMP, or a phosphodiesterase inhibitor. In conclusion, the present studies are consistent with the view that the concentrating defect seen in adrenal insufficiency is at least partly the result of the absence of the permissive effect that adrenal steroids exert on the ADH-induced reabsorption of water across the collecting duct. The absence of adrenal steroids results in a diminished rate of cyclic AMP accumulation in the cells of the collecting duct, either as a result of an augmented activity of cyclic AMP phosphodiesterase or a diminished rate of cyclic AMP generation.

Identification of mineralocorticoid target sites in the isolated rabbit cortical nephron.

Previous evidence suggests that the activity of the mitochondrial enzyme citrate synthase [citrate oxaloacetate-lyase (pro-3S-CH(2)COO --> acetyl-CoA), EC 4.1.3.7] is increased in target tissues upon acute administration of aldosterone. Therefore, an ultramicro assay was established to determine citrate synthase levels in isolated rabbit nephron segments as a means of localizing mineralocorticoid-responsive sites within the renal cortex. The relative citrate synthase activities in normal rabbit segments (per kg of dry tissue) correlated with the metabolic activity of the segments. The order was: distal convoluted tubule > proximal convoluted tubule > cortical thick ascending limb of Henle > cortical collecting duct > pars recta. When these segments were isolated from adrenalectomized rabbits, only the citrate synthase activity in the cortical collecting duct was significantly decreased compared to normal values (3.2 mol of citrate/kg dry wt per hr compared to 7.1; P < 0.001). Furthermore, enzyme activities in segments isolated from adrenalectomized rabbits 90 min after intravenous injection of aldosterone (10 mug/kg) were unchanged from normal or adrenalectomized rabbit tubule values for all segments except the cortical collecting duct. In this segment, aldosterone significantly increased citrate synthase activity compared to adrenalectomized rabbit values (8.1 mol/kg per hr compared to 3.2; P < 0.001), in contrast to the effect of dexamethasone at 10 mug/kg (4.4 mol/kg per hr compared to 3.2; P, NS). Spirolactone SC 26304 administered 30 min prior to injection of aldosterone inhibited the increase in collecting duct citrate synthase activity seen with aldosterone alone (3.4 mol/kg per hr compared to 8.1; P < 0.001). These findings suggest that the collecting duct is the primary target for aldosterone in the renal cortex.