Eccrine mucinous metaplasia associated with an apocrine cystadenoma.

Mucinous metaplasia occurs uncommonly in cutaneous pathology, usually at specialized anatomic locations (genitalia, palms, and soles) and within restricted pathologic contexts (inflammation and trauma). Here, we report a unique case of eccrine mucinous metaplasia associated with an apocrine cystadenoma. A 13-year-old girl had an asymptomatic, 4-mm nodule on the chest. Histopathology demonstrated a typical apocrine cystadenoma in the upper and middle dermis. Adjacent to this lesion was a cluster of coiled eccrine secretory glands, of which the inner layer was almost entirely replaced by benign-appearing cells containing abundant, non-sulfated acid mucopolysaccharides. At 10 months' follow up, there was no recurrence. Our case demonstrates that, very uncommonly, mucinous metaplasia may be associated with a pathogenetically separate, adjacent proliferative adenomatous lesion, in this instance, an apocrine cystadenoma.

Respiratory modulation of human autonomic rhythms.

We studied the influence of three types of breathing [spontaneous, frequency controlled (0.25 Hz), and hyperventilation with 100% oxygen] and apnea on R-R interval, photoplethysmographic arterial pressure, and muscle sympathetic rhythms in nine healthy young adults. We integrated fast Fourier transform power spectra over low (0.05-0.15 Hz) and respiratory (0.15-0.3 Hz) frequencies; estimated vagal baroreceptor-cardiac reflex gain at low frequencies with cross-spectral techniques; and used partial coherence analysis to remove the influence of breathing from the R-R interval, systolic pressure, and muscle sympathetic nerve spectra. Coherence among signals varied as functions of both frequency and time. Partialization abolished the coherence among these signals at respiratory but not at low frequencies. The mode of breathing did not influence low-frequency oscillations, and they persisted during apnea. Our study documents the independence of low-frequency rhythms from respiratory activity and suggests that the close correlations that may exist among arterial pressures, R-R intervals, and muscle sympathetic nerve activity at respiratory frequencies result from the influence of respiration on these measures rather than from arterial baroreflex physiology. Most importantly, our results indicate that correlations among autonomic and hemodynamic rhythms vary over time and frequency, and, thus, are facultative rather than fixed.

Inducible expression of Enterococcus faecalis aggregation substance surface protein facilitates bacterial internalization by cultured enterocytes.

Aggregation substance (AS) is an Enterococcus faecalis surface protein that may contribute to virulence. Using a recently described system for controlled expression of AS in E. faecalis and the heterologous host Lactococcus lactis, experiments were designed to assess the effect of AS on bacterial internalization by HT-29 and Caco-2 enterocytes. AS expression was associated with increased internalization of E. faecalis by HT-29 enterocytes and of L. lactis by HT-29 and Caco-2 enterocytes. Compared to enterocytes cultivated under standard conditions, either cultivation in hypoxia or 1-h pretreatment of enterocytes with calcium-free medium resulted in increased internalization of both E. faecalis and L. lactis (with and without AS expression). Also, AS expression augmented these increases when E. faecalis was incubated with pretreated HT-29 enterocytes and when L. lactis was incubated with pretreated Caco-2 and HT-29 enterocytes. These data indicated that AS might facilitate E. faecalis internalization by cultured enterocytes.

Human responses to upright tilt: a window on central autonomic integration.

1. We examined interactions between haemodynamic and autonomic neural oscillations during passive upright tilt, to gain better insight into human autonomic regulatory mechanisms. 2. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in nine healthy young adults. Subjects breathed in time with a metronome at 12 breaths min-1 (0.2 Hz) for 5 min each, in supine, and 20, 40, 60, 70 and 80 deg head-up positions. We performed fast Fourier transform (and autoregressive) power spectral analyses and integrated low-frequency (0.05-0.15 Hz) and respiratory-frequency (0. 15-0.5 Hz) spectral powers. 3. Integrated areas of muscle sympathetic bursts and their low- and respiratory-frequency spectral powers increased directly and significantly with the tilt angle. The centre frequency of low-frequency sympathetic oscillations was constant before and during tilt. Sympathetic bursts occurred more commonly during expiration than inspiration at low tilt angles, but occurred equally in expiration and inspiration at high tilt angles. 4. Systolic and diastolic pressures and their low- and respiratory-frequency spectral powers increased, and R-R intervals and their respiratory-frequency spectral power decreased progressively with the tilt angle. Low-frequency R-R interval spectral power did not change. 5. The cross-spectral phase angle between systolic pressures and R-R intervals remained constant and consistently negative at the low frequency, but shifted progressively from positive to negative at the respiratory frequency during tilt. The arterial baroreflex modulus, calculated from low-frequency cross-spectra, decreased at high tilt angles. 6. Our results document changes of baroreflex responses during upright tilt, which may reflect leftward movement of subjects on their arterial pressure sympathetic and vagal response relations. The intensity, but not the centre frequency of low-frequency cardiovascular rhythms, is modulated by the level of arterial baroreceptor input. Tilt reduces respiratory gating of sympathetic and vagal motoneurone responsiveness to stimulatory inputs for different reasons; during tilt, sympathetic stimulation increases to a level that overwhelms the respiratory gate, and vagal stimulation decreases to a level below that necessary for maximal respiratory gating to occur.

Pharmacologic preconditioning with monophosphoryl lipid A is abolished by 5-hydroxydecanoate, a specific inhibitor of the K(ATP) channel.

We sought to determine the role of opening of adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP) channel) in monophosphoryl lipid A (MLA)-induced myocardial protection after ischemia/reperfusion (I/R) in rabbit. We used 5-hydroxydecanoate (5-HD), an ischemia-selective inhibitor of K(ATP) channel, to block MLA-stimulated cardiac protection. Four groups of rabbits were studied: group I, MLA-vehicle; group II, MLA; group III, MLA + 5-HD; and group IV, 5-HD only. MLA (35 microg/kg, i.v.) or vehicle were given 24 h before I/R. 5-HD (5 mg/kg) was given 15 min before ischemia. All rabbits underwent 30-min coronary occlusion, followed by 3-h reperfusion. Area at risk was delineated by injection of Evan's blue, and infarct size was determined by tetrazolium staining. Pretreatment with MLA reduced infarct size (percentage of area at risk) from 40+/-8.6% to 15.1+/-1.5%. The infarct size increased to 51.9+/-5.8% with 5-HD in MLA-treated rabbits. 5-HD did not alter infarct size significantly when given in vehicle-treated control rabbits. These data suggest that MLA exerts its protective effect through activation of K(ATP) channel.

Controlled breathing protocols probe human autonomic cardiovascular rhythms.

The purpose of this study was to determine how breathing protocols requiring varying degrees of control affect cardiovascular dynamics. We measured inspiratory volume, end-tidal CO2, R-R interval, and arterial pressure spectral power in 10 volunteers who followed the following 5 breathing protocols: 1) uncontrolled breathing for 5 min; 2) stepwise frequency breathing (at 0.3, 0.25, 0.2, 0.15, 0.1, and 0.05 Hz for 2 min each); 3) stepwise frequency breathing as above, but with prescribed tidal volumes; 4) random-frequency breathing (approximately 0.5-0.05 Hz) for 6 min; and 5) fixed-frequency breathing (0.25 Hz) for 5 min. During stepwise breathing, R-R interval and arterial pressure spectral power increased as breathing frequency decreased. Control of inspired volume reduced R-R interval spectral power during 0.1 Hz breathing (P < 0.05). Stepwise and random-breathing protocols yielded comparable coherence and transfer functions between respiration and R-R intervals and systolic pressure and R-R intervals. Random- and fixed-frequency breathing reduced end-tidal CO2 modestly (P < 0.05). Our data suggest that stringent tidal volume control attenuates low-frequency R-R interval oscillations and that fixed- and random-rate breathing may decrease CO2 chemoreceptor stimulation. We conclude that autonomic rhythms measured during different breathing protocols have much in common but that a stepwise protocol without stringent control of inspired volume may allow for the most efficient assessment of short-term respiratory-mediated autonomic oscillations.

ATP-sensitive potassium channel mediates delayed ischemic protection by heat stress in rabbit heart.

Heat shock protects against myocardial ischemia-reperfusion injury possibly via increased expression of heat shock proteins. The direct evidence of heat shock protein protection in vivo remains circumstantial, and no other new mechanism of protection has been proposed. Recent studies suggest that opening of ATP-sensitive K+ channels (KATP channels) plays an important role in ischemic preconditioning; however, it is not known whether this channel is also important in delayed protection conferred by heat shock. Anesthetized rabbits underwent heat shock treatment by raising core temperature to 42 degrees C for 15 min. Twenty-four hours later, the animals were reanesthetized and subjected to regional ischemia-reperfusion. The specific KATP channel blockers glibenclamide (0.3 mg/kg i.p.) and sodium 5-hydroxydecanoate (5HD; 5 mg/kg i.v.) were used to block the channel function. The drugs were administered at two different times, either pre-heat stress or preischemia. Infarct size was determined by triphenyltetrazolium chloride staining. The 72-kDa heat shock protein (HSP 72) was measured by Western blots. Our results show that heat shock produced a marked reduction in infarct size (39.4 +/- 8.1 to 14.3 +/- 2.5% of risk area, P < 0.05). Glibenclamide and 5HD completely abolished heat shock-induced reduction in infarct size (42.3 +/- 0.32 and 33.7 +/- 4.8%) when given before ischemia-reperfusion; however, these antagonists failed to block protection when administered before the onset of heat shock. Furthermore, the enhanced expression of HSP 72 in heat shock groups was not diminished by glibenclamide or 5HD, suggesting a lack of a direct role of this protein in conferring cardiac protection by heat shock. The complete blockade of cardiac protection by glibenclamide and 5HD strongly suggests that opening of this channel is a very important component of heat shock-induced ischemic protection in rabbit hearts.

Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope.

BACKGROUND: Autonomic and particularly sympathetic mechanisms play a central role in the pathophysiology of vasovagal syncope. We report direct measurements of muscle sympathetic nerve activity in patients with orthostatic vasovagal syncope. METHODS AND RESULTS: We studied 53 otherwise healthy patients with orthostatic syncope. We measured RR intervals and finger arterial pressures and in 15 patients, peroneal nerve muscle sympathetic activity before and during passive 60 degree head-up tilt, with low-dose intravenous isoproterenol if presyncope did not develop by 15 minutes. We measured baroreflex gain before tilt with regression of RR intervals or sympathetic bursts on systolic or diastolic pressures after sequential injections of nitroprusside and phenylephrine. Orthostatic vasovagal reactions occurred in 21 patients, including 7 microneurography patients. Presyncopal and nonsyncopal patients had similar baseline RR intervals, arterial pressure, and muscle sympathetic nerve activity. Vagal baroreflex responses were significantly impaired at arterial pressures below (but not above) baseline levels in presyncopal patients. Initial responses to tilt were comparable; however, during the final 200 seconds of tilt, presyncopal patients had lower RR intervals and diastolic pressures than nonsyncopal patients and gradual reduction of arterial pressure and sympathetic activity. Frank presyncope began abruptly with precipitous reduction of arterial pressure, disappearance of muscle sympathetic nerve activity, and RR interval lengthening. CONCLUSIONS: Patients with orthostatic vasovagal reactions have impaired vagal baroreflex responses to arterial pressure changes below resting levels but normal initial responses to upright tilt. Subtle vasovagal physiology begins before overt presyncope. The final trigger of human orthostatic vasovagal reactions appears to be the abrupt disappearance of muscle sympathetic nerve activity.

Effectiveness of subcutaneous dihydroergotamine by home injection for migraine.

The effectiveness of dihydroergotamine administered by home subcutaneous injection by the patient or family for severe headache attacks was assessed retrospectively in 51 patients. Average follow-up was 21 weeks. Twenty-one patients had intermittent migraine attacks, 27 had transformed migraine with chronic daily headache, and 3 had chronic tension-type headache. Of the 51 patients taught home injection, 35% had an excellent overall response, 18% had a good response, 12% had a poor response but continued to use dihydroergotamine, and 35% had discontinued dihydroergotamine use. Side effects were the main reason for stopping dihydroergotamine. These included nausea or vomiting or both, limb pain or numbness or both, chest or throat tightness or both, and soreness at the injection site. Thirty-three patients (65%) continued to use dihydroergotamine at the end of the follow-up period. In patients who previously required injections from medical personnel for headache crises and in whom home injection of dihydroergotamine was effective, a dramatic reduction occurred in hospital emergency room and physician office utilization. Dihydroergotamine use by home injection can be an effective treatment for a significant proportion of patients with severe migraine including patients with transformed migraine and medication overuse.

On the interaction of the liposomal membrane with blood components.

Liposome-encapsulated hemoglobin (LEH) has been shown to be a viable candidate as a blood replacement. However, few data have been presented as to how LEH interacts with normal blood components. Liposomes were prepared from egg lecithin, cholesterol, and dicetyl phosphate or phosphatidic acid, and mixed with fresh blood plasma or whole blood. Erythrocyte osmotic fragility, prothrombin time (extrinsic coagulation efficiency), activated partial thromboplastin time (intrinsic coagulation efficiency), plasma clot stability in urea (fibrin stabilizing factor), and clot retraction (platelet activation) were measured. Although liposomes were found to bind extensively to erythrocytes, all tests indicated that the liposomes had no significant adverse effects, provided that normal levels of plasma Ca++ were maintained. The ability of liposomes to absorb Ca++ from the plasma was related directly to the amount of dicetyl phosphate or phosphatidic acid present and thus, presumably, to the presence of negatively charged species in the membrane. The mechanics of deformation of the LEH membrane were investigated by encapsulating Hemoglobin S in liposomes. Liposomes containing Hemoglobin S were found to sickle when deoxygenated, but not liposomes containing normal hemoglobin. Shape analysis of sickled liposomes yielded a deforming stress of 10(6) dynes/cm2, about 50 times greater than the reported limit for shear elasticity of the erythrocyte membrane.

Long-term effect of cromolyn sodium on nonspecific bronchial hyperresponsiveness: a review.

Long-term treatment with cromolyn sodium will reduce airway hyperresponsiveness in patients with bronchial asthma. Short-term use of cromolyn sodium (less than 6 weeks) is effective in preventing seasonal increases in allergen-induced hyperresponsiveness. Cromolyn sodium therapy for greater than 12 weeks appears to be beneficial in reducing baseline hyperresponsiveness. The effect of cromolyn sodium on bronchial hyperresponsiveness may result from its ability to stabilize mast cells. Other contributory properties of cromolyn sodium are reviewed.

Spontaneous mutation in the male gamete as a cause of hemophilia A: clarification of a case using DNA probes.

The carrier status of two sisters of the mother of a hemophilic boy was clarified by the use of DNA probes in a family with a single case of hemophilia A and no family history of the disease. The extragenic polymorphic site demonstrated by probe DX13 (locus DXS15) and the intragenic polymorphic site demonstrated by BgI I digestion and a factor VIII partial cDNA probe indicated that the mother of the index case carried a mutation in the X-chromosome received from her nonhemophilic father rather than the X-chromosome received from her mother. In spite of equivocal coagulation data, the mother's two sisters were shown not to be carriers of hemophilia A.

Abelson murine leukemia virus variants with increased oncogenic potential.

A number of strains of Abelson murine leukemia virus (A-MuLV) with various abilities to transform cells have been identified. Among these is the A-MuLV-P90 strain, a mutant derived from A-MuLV-P120 that encodes an A-MuLV protein missing sequences that are normally present at the extreme carboxy terminus of P120 (N. Rosenberg and O. N. Witte, J. Virol. 33:340-348, 1980). This virus transforms NIH 3T3 cells efficiently but does not transform a high frequency of lymphoid cells in vitro or in vivo. In this communication, we show that of the relatively few tumors induced by A-MuLV-P90 nearly all contained new variant viruses that stably expressed either larger or smaller A-MuLV proteins. Strains that expressed larger A-MuLV proteins behaved like A-MuLV-P120 in transformation assays, whereas those expressing smaller A-MuLV proteins induced a high frequency of tumors after a short latent period in vivo but failed to transform large numbers of lymphoid cells in vitro. Thus, these latter viruses separated the requirements for in vitro transformation of lymphoid cells from those for tumor induction. All of the variants differed from A-MuLV-P90 in the carboxy-terminal region of the A-MuLV protein, suggesting that sequences in this region play a key role in the ability of the virus to interact with hematopoietic cells in vivo and in vitro.

Protein stabilization explains the gag requirement for transformation of lymphoid cells by Abelson murine leukemia virus.

The single protein encoded by Abelson murine leukemia virus is a fusion of sequence from the retroviral gag genes with the v-abl sequence. Deletion of most of the gag region from the transforming protein results in a virus capable of transforming fibroblasts but no longer capable of transforming lymphoid cells. Smaller deletions in gag reveal that p15 gag sequences are responsible for this effect, whereas deletion of p12 sequences had no effect on lymphoid transformation. In transformed fibroblasts, p15-deleted and normal proteins had similar activities and subcellular localization. When the p15-deleted genome was introduced into previously transformed lymphoid lines, its protein product exhibited a marked instability. The tyrosine-specific autophosphorylation activity per cell was less than 1/20th that of the nondeleted protein. Although pulse-Ia-beling showed that the p15-deleted protein was synthesized efficiently, immunoblotting demonstrated that its steady-state level was less than 1/10th that of the nondeleted Abelson protein. The specific instability of the p15-deleted protein in lymphoid cells explains the requirement of these sequences for lymphoid but not fibroblast transformation.

Prediction of the widths of unerupted canines and premolars.

The purpose of this study was to develop, with simple linear regression analysis, equations that could accurately predict the mesiodistal widths of unerupted canines and premolars in both arches of the mixed dentition patient. Clinically useful prediction equations were developed and tested on a sample of orthodontic patients. Performance of the equations in patients was satisfactory. Charts and suggestions for completing a tooth size-arch length analysis in the patient with a mixed dentition were discussed.

Marathon: a life-and-death experience.

Therapists have a great need for techniques capable of provoking change in their clients. Generally, people resist change and need incentives to accomplish it. The tools to effect change are few. Therefore, the value of the theme Marathon experience is that it can be both innovative and piercing. Many clients need to have the drama of their own lives connected to a meaningful plot. The theme Marathon experience can do this. It exerts an influence on the emotional, cognitive and behavioral aspects of the participants and connects their past to the present and future, allowing them to see clearly the futility of a life of chemical dependence.

Diabetic patients on hemodialysis.

In general, individuals who have a chronic illness must make major emotional and physical adjustments. Do patients forced to cope with two chronic conditions make these adjustments with greater difficulty or with increased ease? This study compared diabetic and nondiabetic patients having end-stage renal disease and examined how individuals already ill with diabetes adapt to the additional stress of hemodialysis treatment.