Intraluminal pressure modulates vascular contractility of perfused mesenteric resistance arteries. Altered response in hypertension.

Intraluminal pressure may affect vascular contractility in both normotension and hypertension. To test this hypothesis, we studied mesenteric resistance arteries from normotensive humans as well as normotensive (WKY) and spontaneously hypertensive (SHR) rats (internal diameter 214 +/- 27, 201 +/- 6, and 172 +/- 6 microns, mean +/- SEM at 10 mm Hg). Vessels were mounted on glass cannulas and perfused in organ chambers filled with buffer solution at intraluminal pressures of 10 to 120 mm Hg; vasomotion was measured using a video dimension analyzer. Under baseline conditions (10 mm Hg), wall thickness was 36 +/- 4 microns in humans, 32 +/- 4 microns in WKY, and 47 +/- 2 microns in SHR (P less than .001). With increasing pressure, the diameter of human vessels increased up to 25 mm Hg and remained constant at higher pressures. In contrast, resistance arteries of normotensive and hypertensive rats exhibited an almost linear increase in diameter over the whole pressure range. In SHR, the pressure-diameter relationship was much flatter than that of WKY, indicating reduced compliance. In human arteries, the contraction to KCl was maximal at 25 mm Hg and averaged 40 +/- 6%. Both above and below 25 mm Hg, the response declined to a minimum of 17 +/- 2% at 120 mm Hg (P less than .01). Similar results were obtained in WKY rats. In contrast, the contractile response in SHR remained maximal over the entire pressure range studied (65 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of intermittent exposure to cold on the development of hypertension in the rat.

Continuous exposure to a cold (5 degrees C) environment has been shown to induce hypertension in rats. The total time required for the first significant elevation of blood pressure is dependent on a number of factors, including the ambient temperature and the weight of the rat at the time of exposure to cold. The present study was also concerned with the minimal time of daily exposure to cold that would result in a significant elevation of blood pressure. To achieve this, we used four groups of rats. One was exposed to cold for 4 h daily (09:00 to 13:00), a second group was exposed to cold for 8 h daily (09:00 to 17:00), and a third was exposed for 24 h daily. The fourth group remained at 25 degrees C. Systolic blood pressures of the group exposed to continuous cold became elevated significantly above pre-cold exposure level within 2 weeks of cold exposure. Blood pressures of the groups exposed to cold for 4 and 8 h daily became elevated significantly above the level of the warm-adapted control group by day 27 of exposure to cold, but failed to reach the level of the chronically cold-exposed group even after 42 days of exposure to cold. There was a sigmoid-type relationship between the hours per day exposed to cold and systolic blood pressure at the end of the experiment. Thus, graded elevations of systolic blood pressure occur with increasing daily duration of exposure to cold.(ABSTRACT TRUNCATED AT 250 WORDS)


Dissociation of hypertension and genetically enhanced cell growth capacity in skin fibroblasts of F2 hybrid spontaneously hypertensive rats/Wistar-Kyoto rats.

Skin fibroblasts from newborn spontaneously hypertensive rats (SHR) grow faster in culture than Wistar-Kyoto rat (WKY) cells. Similar results have been described for vascular smooth muscle cells from prehypertensive and adult SHR. This suggests the existence of an intrinsic abnormality in vascular and nonvascular cells of mesodermal origin affecting cell growth control in those rats. In an attempt to determine the relation between high blood pressure and this trait, we cultured skin fibroblasts from adult SHR, WKY, F1, and F2 hybrid SHR/WKY populations by explant technique. Their growth capacity was determined by culture well DNA doubling time and by [3H]thymidine incorporation. Adult SHR fibroblasts grew more quickly (doubling time [DT] = 37.2 +/- 2.3 h, n = 8) than WKY ones (DT = 53.9 +/- 3.6 h, n = 6). Female SHR were crossed with male WKY to produce an F1 and an F2 hybrid generation presenting a Mendelian distribution of blood pressure. Skin fibroblasts were cultured from 21 rats belonging to the highest and the lowest blood pressure groups. No difference was observed between the two groups in either growth (DT = 47.5 +/- 4.1 h, n = 11 v DT = 44.6 +/- 3.2 h, n = 10) or epidermal growth factor-induced [3H]thymidine incorporation. These observations suggest that the increased growth capacity observed in SHR is not a determinant of high blood pressure initiation but may be involved in early cardiovascular enlargement.


Concomitant release of renin, angiotensin I, and angiotensin II during superfusion of human juxtaglomerular cell tumor.

Increasing evidence indicates that angiotensin II can be formed by juxtaglomerular cells (JGC) and cosecreted with renin. We investigated the existence of this local renin-angiotensin system in a human JGC tumor, using an in vitro superfusion. The JGC tumor was found concomitantly to release renin and angiotensin I and II. Sequential addition of atrial natriuretic peptide, dopamine, and a somatostatin analog in the superfusion did not affect renin or angiotensin I and II release. The data provide evidence that the human JGC tumor in vitro generates angiotensin II, and supports its possible role as a local in vivo regulator of kidney function.


Prevalence of left ventricular hypertrophy and cardiac arrhythmias in borderline hypertension.

Seventy-eight men with borderline hypertension according to the World Health Organization criteria underwent echocardiographic examination, followed by simultaneous ambulatory blood pressure and electrocardiographic monitorings for 24 h. The prevalence of echocardiographic left ventricular hypertrophy was 16.6% (13/78). Borderline hypertensives with left ventricular hypertrophy had more supraventricular (P less than .001) and ventricular ectopic beats (P less than .001) than normotensive controls and borderline hypertensives without cardiac involvement. Furthermore, ventricular ectopic activity was significantly related to left ventricular mass (r = 0.58, P less than .05) in borderline hypertensives showing echocardiographic evidence of left ventricular hypertrophy. Our findings suggest that noninvasive assessment of target organ status, including echocardiography, should be employed to optimize risk stratification in borderline hypertension.


Current status of chairpersons in physical medicine and rehabilitation.

There are currently 77 academic departments, divisions or units of physical medicine and rehabilitation (PM&R) in the United States. The authors conducted a survey to develop a profile of the current chairpersons of PM&R, as well as to assess the short- and long-term needs of the field. The survey addressed basic demographic information as well as the level of formal training and/or experience in various management, patient care and academic areas. The level of satisfaction with various aspects of the position such as workload, relationship with the university and role as a researcher were also measured. The chairpersons were asked when they plan to vacate their position and if they felt there were any members of their faculty who are qualified and ready to assume a chairperson position. Those that identified a qualified individual were then asked whether the person had formal training and/or experience in the various management, patient care and academic areas. The results indicate that, although the chairpersons have a high level of job satisfaction with respect to the challenge of the position and their administrative and supervisory roles, they are least satisfied with their role as a researcher. The field must be concerned with this finding, because academic PM&R units in the United States will experience a substantial change in leadership by the end of the 20th century. Approximately 39% of the current chairpersons who returned the questionnaire are planning to step down by 1999, with an additional 37% unsure when they will vacate the position.(ABSTRACT TRUNCATED AT 250 WORDS)


Standardized nerve conduction studies in the upper limb of the healthy elderly.

Nerve conduction studies are increasingly being performed on elderly individuals; however, no standardized data for the elderly population exists to provide an accurate interpretation of electrodiagnostic findings. The purpose of this study was to provide standardized data in the healthy elderly for the nerves of the upper limb that are routinely chosen for study by electromyographers. Nerve conduction studies were performed prospectively in one upper limb of 155 carefully screened healthy elderly individuals between the ages of 60 and 95 years. Upper limb temperature was controlled to limit the influence of temperature on the measured conduction parameters. Standard nerve conduction techniques using constant measured distances were applied to evaluate the median, ulnar and radial nerves. A normative electrodiagnostic database for elderly individuals was established in this study. The mean nerve conduction parameters of this healthy elderly population compared favorably with existing literature values for younger populations. However, age had a statistically significant but low strength effect on all ulnar nerve conduction velocities and distal latencies as well as the distal sensory amplitudes of all three nerves. Gender had a greater effect than age on these parameters as well as on median sensory distal latency. Other median motor and sensory conduction parameters along with radial sensory distal latency were not significantly related to age or gender based on two-way analysis of variance.


Analysis of mechanical and metabolic factors in the gait of congenital below knee amputees. A comparison of the SACH and Seattle feet.

Prosthetic feet have been developed with the intention that they deform during the first half of the stance phase to store energy that can be released at the end of stance and contribute to push-off. The purpose of this study was to examine the three-dimensional kinematics and kinetics of gait and metabolic energy cost in children and adolescents with below-knee amputations using the SACH and Seattle prosthetic feet. The metabolic test consisted of an 8-min walk around an oval track while expired gases were collected and analyzed. The biomechanical test consisted of 10 walking trials: 5 for each of the prosthetic and sound limbs. Stance and swing phase moments and powers were calculated for both the prosthetic and sound limbs. A four-camera VICON system recorded movements of the limb segments to calculate joint kinematics, and these were combined with ground reaction force data in a three-dimensional model to determine moments and powers about the hip, knee and ankle joints. The Seattle foot produced a small increase in stride length, which led to a small increase in walking velocity. Biomechanical data revealed that the Seattle foot was less resistant to passive dorsiflexion in midstance, and although there was no effect on the work done across the prosthetic ankle, a knee flexor moment dominated the stance phase when the SACH foot was tested, whereas the Seattle foot allowed a normal extensor moment. The profile of work was unaffected by the type of foot. On the sound side, the hip produced most of the positive work while the ankle output was below normal.(ABSTRACT TRUNCATED AT 250 WORDS)


Lack of effect of amitriptyline in murine myotonia.

Amitriptyline, a tricyclic antidepressant, has been reported to diminish signs of human myotonic muscular dystrophy, but has not been examined in other myotonias. Normal and myotonic (ADRmto) mice were injected acutely with either amitriptyline, phenytoin, procainamide or 0.9% saline. In addition, two groups of myotonic mice were injected chronically with either 0.9% saline or amitriptyline for 28 days. Behavior, assessed before injection using a "drop test," was re-evaluated at 30-min intervals for up to 180 min postinjection, as well as at the end of the 28-day chronic trial. If improvement in behavior was noted, the mice were then evaluated with insertional needle electromyography (EMG) and in vitro contractility (maximal tetanic tension and relaxation time) studies. Neither acute nor chronic amitriptyline administration had any beneficial effect on behavior, EMG or contractile parameters in myotonic mice. Phenytoin abolished abnormal EMG activity and improved behavior. Procainamide improved behavior and contractility parameters but had no effect on EMG. These results confirm that the myotonic mouse is responsive to classic antimyotonic agents, but not to amitriptyline.


Linearity and reliability of the IEMG v torque relationship for the forearm flexors and leg extensors.

The purpose of this investigation was to examine the linearity and reliability of the surface integrated electromyogram (IEMG) v isometric torque relationship for the leg extensors and forearm flexors. Nine men and four women (mean age +/- SD = 22 +/- 2 yr) volunteered for this investigation. Isometric testing was conducted on a Cybex II isokinetic dynamometer with the lever arm at 0.785 rad (45 degrees) below the horizontal plane for the leg extensors and in the vertical plane for the forearm flexors. Bipolar surface electrodes were used to record IEMG values from the vastus lateralis and biceps brachii. To examine test-retest reliability, two test sessions, separated by a minimum of 48 h, were performed. The test-retest linearity of the IEMG v torque relationship ranged from r2 = 0.77 to 0.96 and 0.55 to 0.94 for the forearm flexors and r2 = 0.81 to 0.98 and 0.83 to 0.98 for the leg extensors. The slope values were not significantly different (P > 0.05) between sessions and were correlated (intraclass correlation coefficients) at R = 0.86 (standard error of estimate (SEE) = 5.77 microV.Nm-1, 31% of the mean) and R = 0.97 (SEE = 0.27 microV.Nm-1, 12% of the mean) for the forearm flexors and leg extensors, respectively. The test-retest maximal torque values were 57.73 +/- 22.57 Nm and 58.14 +/- 22.81 Nm (R = 0.99; SEE = 2.39 Nm) for the forearm flexors and 187.79 +/- 55.98 Nm and 195.42 +/- 56.27 Nm (R = 0.96; SEE = 22.62 Nm) for the leg extensors (nonsignificant differences; P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Patient awareness of physical medicine and rehabilitation.

The present study examined the extent to which patients referred to a specialist in physical medicine and rehabilitation (PM&R) could correctly identify the name or essential scope of the specialty the physiatrist practiced. The hypothesis, based on the author's experiences as a staff physiatrist, was that most patients would not be aware of the name and scope of the specialty of physical medicine and rehabilitation. This prospective study involved the administering of a questionnaire to 202 consecutive referrals to a University-affiliated PM&R outpatient clinic. Of the respondents, 19% were able to correctly identify that the physician they were referred to was either a PM&R specialist, a physical medicine specialist, a rehabilitation specialist or a physiatrist. Among the incorrect responses, orthopedist, neurologist and rheumatologist were most prevalent, and 33% of the respondents thought the physiatrist performed surgery. The implications of the findings are discussed. There continues to be a need to educate the public about the scope of practice of physiatry.


Hemiparesis in HIV infection. Rehabilitation approach.

Persons with acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection demonstrate a wide array of central nervous system impairments and may be at a significantly increased risk for cerebrovascular disease. Cerebrovascular disease can be the first manifestation of HIV infection and may be associated with a treatable etiology. Anticipating more referrals for HIV-related physical disability, we detail the rehabilitation management of three persons with HIV infection and hemiparesis. Onset of hemiparesis ranged from just before to 24 months after an AIDS-defining illness. No specific underlying etiology was identified in two of three patients, consistent with previous observations. Rehabilitation interventions included lower and upper extremity orthoses, assistive devices to aid gait and activities of daily living, therapeutic exercise and use of antispasticity medication. All patients made at least mild, temporary gains in functional status. Survival ranged from 3 to >6 months from initial contact with rehabilitation services. Neurologic and nonneurologic considerations in the rehabilitation of persons with HIV infection are discussed. We conclude that selected individuals with HIV infection and hemiparesis can benefit from rehabilitation intervention. HIV infection should be considered in any young adult presenting with stroke.


Mirror movements in the alien hand syndrome. Case report.

The alien hand syndrome has been associated with different descriptions of abnormal motor behavior. We report on two patients with transient left hemiparesis who remained with limb apraxia and were particularly impaired by a variety of involuntary skilled movements of their apractic limb. After the report and a review of the literature, we discuss the presence of one type of abnormal movement observed in this syndrome. These movements resemble the mirror movements seen in the normal development of motor control and in some pathologic conditions later. Their appearance in the alien hand syndrome seems to demand both intrahemispheric and interhemispheric motor pathway damage.


Clonidine in the treatment of brainstem spasticity. Case report.

This report describes a patient who developed spasticity after a medullary infarct. No improvement in her spasticity was achieved by baclofen therapy and the side effects of the drug necessitated its gradual withdrawal. Recent reports of the success of clonidine in the management of spasticity due to spinal cord injury prompted an attempt at clonidine therapy. When clonidine therapy was initiated, the patient responded rapidly with both subjective and objective improvements in her spasticity. This case suggests a potential role for clonidine in the treatment of spasticity resulting from brainstem infarction.


Walker modification for ventilator-assisted individuals. Case report.

A case is presented of a 53-yr-old ambulatory ventilator-dependent individual who demonstrated that functional ambulation could be possible with a modified rolling walker. The patient used intermittent positive pressure ventilation delivered by noninvasive methods 24 h a day. For potentially ambulatory ventilator users, intensive rehabilitation and the use of a modified walker can improve medical, psychological and social status and permit the resumption of vocational activities. Mouth intermittent positive pressure ventilation is the method of choice for daytime ventilatory support during ambulation for individuals with severe chronic alveolar hypoventilation because of predominantly restrictive pulmonary syndromes.


AIDS epidemiology and pathology. Implications for intensive care units.

The acquired immunodeficiency syndrome (AIDS) evolves from infection with the human immunodeficiency virus (HIV). The HIV attacks the hosts' immune and neuroendocrine systems, rendering the host susceptible to a myriad of chronic and acute conditions requiring intensive care. This article reviews epidemiologic and pathologic trends associated with HIV infections that have the potential to increase demands for admission to intensive care units. Research describing potential predictors of survival among patients with HIV-related conditions is also described. In addition, possible implications for practice, education, and research are discussed.


Opportunistic infections and pharmacology.

The most common acute complication in HIV infection is likely to be one of the many possible opportunistic infections caused by immunodeficiency. These infections may be the index diagnosis of AIDS or occur in previously diagnosed patients as additional problems. Monitoring for the symptoms of disease and monitoring patients while undergoing treatment are frequently included in nursing care. This article discussed the diagnosis and treatment of some of the more common of the major opportunistic infections seen in AIDS.


Infection prevention and control.

Nurses are clearly at risk for exposure to HIV through blood and body fluids, and they frequently use needles and sharp objects. In addition, critical care patients are at high risk for nosocomial infections due to other etiologic agents. This article addresses reducing the risk of infection for both nurses and patients using a variety of strategies.


Psychosocial and neuropsychiatric care.

Psychosocial problems of persons with HIV disease require knowledge and skill in psychosocial assessment, suicide risk assessment, crisis intervention and various other therapeutic modalities, provision of social and community resources, and spiritual care. Neuropsychiatric problems require knowledge and skill in neurologic, cognitive, and behavioral assessment and supportive care. Families and partners have needs commensurate with those of the person with HIV disease.


The HIV epidemic. Ethical issues for the next decade.

The HIV epidemic and ethical issues will continue to be a major topic of discussion over the next decade. It is now evolving into a new phase and we are experiencing a change or shift in the populations that are affected. This article focuses on the issues of early intervention, access to care, and the continuum of care including a discussion of case management, the changing populations, drug trials, and issues surrounding confidentiality.


Nursing effectiveness research and patient outcomes. A challenge for the second HIV/AIDS decade.

The need to focus on the nursing care of the acute and chronically ill HIV-infected person is made apparent by an examination of recent data on the prevalence of this disease. A nursing system framework of quality of care is proposed, which includes patient problems (inputs), nursing care activities (processes), and patient outcomes (outcomes). Examples from ongoing research are provided.


Women in the HIV epidemic.

In the United States, the majority of women with HIV/AIDS are women whose lives have been touched by injection drug use--their own or that of their sexual partners. The pattern of opportunistic infections in women is more similar to that of injection drug users than that of homosexual men. Specific complications associated with a woman's reproductive tract include persistent Candida vaginitis, human papillomavirus infections, cervical dysplasias, and, possibly, pelvic inflammatory disease. Childbearing decisions for women with HIV infection are complex and culturally mediated. Meeting the challenge of providing high quality services to women with HIV infection requires major changes in the service delivery system.


Pediatric HIV/AIDS.

The number of children infected with HIV is growing, and new treatments are extending their survival. Nurses, including pediatric intensive care nurses, more frequently have to care for HIV-infected children. This article discusses the transmission of HIV in children, pediatric manifestations of the disease, staging, treatment, and prophylaxis. The complications, treatment, and psychosocial and ethical issues of the child with HIV in the pediatric intensive care unit are examined.


Caring for the adolescent with HIV infection or AIDS in the critical care setting.

Caring for the adolescent with HIV infection or AIDS in the critical care setting is challenging. This article discusses medical treatments for HIV, aspects of adolescent development that influence their behaviors, certain behaviors that put adolescents at risk for HIV acquisition, ethical and legal concerns for caring for this population, nursing implications for care, and the needs of nurses caring for this population.


Neonatal nursing assessment by functional health patterns.

This article provides nurses who care for infants with a tool to document both physical examination and nursing assessment. Specific information to gather data and where to organize initial data are described. This tool also accommodates documentation of the first minutes of assessment and treatment provided when delivering care to critically ill infants on admission to the unit. In addition, it provides a means of further documenting nursing assessment information at a later time (e.g., psychosocial needs). The functional health patterns are a framework to organize the nursing assessment of the neonate and his or her family, and this assessment is the data base for both nursing diagnosis and individualized care planning.


The drug-exposed infant.

Drug use is a widespread problem within our society. This problem is becoming more prevalent within the perinatal population, thus affecting the neonatal population. This article explores the effects of alcohol, cocaine, and opiates on the pregnancy and neonatal outcome.


Group B streptococcal infection in the newborn.

This article reviews the immunologic and microbiologic characteristics of the group B streptococcal organism, perinatal acquisition, clinical presentation, and therapy. A discussion of immunoglobulin transfusion therapy is included, and a case study is presented.


Neonatal seizures.

Seizures are a frequent symptom seen in intensive care nurseries and may be the only sign of a central nervous system disorder in the neonate. The clinical manifestations of neonatal seizures are widely variable and may be indicative of alternate pathophysiology. The advent of portable video electroencephalographic monitoring has improved the ability to correlate clinical behaviors with electrocortical activity and may facilitate diagnosis. The ability to accurately recognize seizures and determine their cause is crucial to providing treatment.


New trends in neonatal mechanical ventilation.

Advances in technology have produced more sophisticated, diverse modes of mechanical ventilation. Efforts to reduce neonatal morbidity and mortality have led clinicians to use a myriad of ventilatory support modalities. It is imperative that critical care nurses become aware of the indications, advantages, and disadvantages of the new modes of ventilatory support. This article reviews respiratory physiology and presents new trends in neonatal mechanical ventilation.


Surfactant replacement therapy in newborns with hyaline membrane disease.

This article discusses the use of surfactant replacement therapy in the management of neonates with hyaline membrane disease (HMD). Included is an overview of HMD, current treatment modalities, a case presentation, nursing implications for managing the infant with HMD, and a nursing care plan. Administration of surfactant is discussed, along with implications for nursing research.


Cardiac transplantation in early infancy.

Congenital heart disease (CHD) encompasses a full spectrum of severity, ranging from physiologically insignificant (those lesions ameliorated over time without surgical or medical intervention) to those lesions that result in certain death in early infancy. Recent attempts at heart and heart-lung transplantation and surgical palliation have provided options for families of infants at the deadly end of this spectrum. The purpose of this article is to outline the process of one form of intervention--heart replacement during early infancy. The main concerns following transplantation are rejection and infection, but survival rates after transplantation show a good 5-year prognosis in this young age group.


Neonatal pain management.

Neonatal pain management is a challenge for the clinician. Research is just beginning to uncover the neonates' capability of expression of pain, explore pharmacologic management strategies, and identify the spectrum of intrusions that may precipitate pain or distress in the critically ill neonate. This article reviews the neonatal biologic, behavioral, and physiologic responses to pain and describes recommendations for clinical management and decision-making.


Intracerebral arteriovenous malformations presenting as neonatal congestive heart failure.

Intracerebral arteriovenous malformations (AVM) are a complex medical emergency in neonates. AVMs are congenital communications between the arterial and venous circulation. Occurring early in gestation, they may enlarge over time, promulgating a left-to-right shunt. This volume overload can present as severe congestive heart failure or as pronounced shock. This article discusses the pathophysiology, clinical presentation, diagnostic modalities, treatment regimens, nursing implications, and complications of cerebral AVMs. A case study is also presented.


Citalopram and 8-OH-DPAT attenuate nicotine-induced excitation of central noradrenaline neurons.

Previous electrophysiological studies have demonstrated that nicotine, intravenously administered, excites noradrenergic neurons in the locus coeruleus (LC) indirectly by releasing excitatory amino acids (EAA). In the present study the excitatory action of nicotine was inhibited by treatment with the selective 5-HT re-uptake inhibitor citalopram or the 5-HT1A receptor agonist 8-OH-DPAT. It is proposed that the antagonism between nicotine and citalopram or 8-OH-DPAT reflects an interaction between endogenous EAA, e.g. glutamate, and 5-HT. The results may, on a cellular basis, explain the attributed effectiveness of drugs that facilitate serotonergic neurotransmission in promoting smoking cessation.


The effect of chronic unpredictable stress on locomotor and exploratory activity in male rats with different endogenous prolactin levels.

The probable role of prolactin (PRL) on the behavioral responses evoked by chronic unpredictable stress (CUS) was studied in adult male rats. Three experiments were performed examining the effect of CUS on behavioral performance in: (i) intact rats with normal endogenous PRL levels, (ii) rats with high endogenous PRL levels, and (iii) rats with low endogenous PRL levels. Behavioral parameters studied were: locomotion, head-dipping, rearing and grooming. Endocrine parameters studied were: PRL and corticosterone (C) plasma concentrations. In Experiment (i) results showed that CUS inhibited significantly locomotion, head-dipping and rearing activity. No variations in PRL plasma levels were found but a significant increase in C was detected. In Experiment (ii) the hyperprolactinaemia induced by pituitary transplants in the kidney capsule blocked partially the inhibition of locomotion due to CUS. No modifications on head-dipping, rearing and grooming were observed. PRL levels in these rats were consistently high as expected and CUS regimen did not change the hormone concentrations in blood. The C response due to CUS, however was completely blocked in the pituitary-implanted group. In Experiment (iii), repeated treatment with bromocriptine (5 mg/kg i.p.) significantly increased the inhibitory effect of CUS on locomotion, head-dipping and rearing. Grooming was also decreased in CUS-treated rats. PRL levels in these animals was low as expected and the C response due to CUS was significantly increased. Results give support to the concept that PRL may have a regulatory role in CUS.


Changes in body temperature markedly affect striatal dopamine release and metabolism: an in vivo study.

Dopamine release and metabolism in the corpus striatum increased markedly when the core body temperature of anesthetized rats was increased from 35 degrees to 41 degrees C while temperatures below 34 degrees were associated with a marked attenuation of dopamine release. These observations may have clinical relevance in cases where alterations in body temperature are associated with extrapyramidal dysfunction.


L-dopa infusion mode differentially affects corpus striatal dopamine efflux in the presence of reserpine.

In the present experiment we tested the effects of L-DOPA upon dopamine (DA) efflux in vitro from superfused corpus striatal tissue fragments in medium containing reserpine. The purposes of this experiment were first, to evaluate the effects of differing infusion modes of L-DOPA upon DA efflux under conditions in which DA storage capacity has been diminished, and second, to compare this L-DOPA stimulated DA efflux with that of other putative DA secretagogues such as amphetamine and potassium. No differences were obtained in stimulated DA efflux between superfusions performed in the presence or absence of reserpine (10 microM) in the medium when L-DOPA (5 microM) was infused in a continuous (70 minute) mode during the superfusion. In contrast, a continuous infusion of either amphetamine (10 microM) or high potassium (30 mM) resulted in significantly greater stimulated DA efflux in superfusions performed with reserpine in the medium. In addition, when L-DOPA (5 microM) was administered for a brief 10-minute infusion period, a significantly greater stimulated DA efflux was obtained with superfusions containing reserpine in the medium. These results suggest that the mode of L-DOPA infusion may be an important factor in regulating DA release under conditions of diminished DA storage capacity.


Blood-CSF barrier permeability and central nervous system immunoglobulin G in schizophrenia.

The ratio of albumin in cerebrospinal fluid (CSF) to serum may serve as an index of the integrity of the blood-CSF barrier, with increases in this ratio indicating increased permeability. The ratio of immunoglobulin G (IgG) in CSF to serum (divided by the albumin ratio to correct for variance in blood-CSF permeability) represents an index of the endogenous production of IgG in the central nervous system (CNS), with increases reflecting a possible infectious and/or autoimmune process stimulating central IgG synthesis. We analyzed simultaneously collected CSF and serum samples from 46 schizophrenic subjects, 8 of whom were studied both on and off neuroleptic treatment, and samples from 20 normal controls. The data indicated increases in CSF/serum albumin ratios or CSF/serum IgG indices in 22% and 20%, respectively, of the schizophrenic patients. Only 3 patients showed elevations in both indices. Comparison of values on and off neuroleptics indicated no significant effect of neuroleptics on these indices.


Dose of dialysis: what index?

Wider patient acceptance criteria in hemodialysis (HD) programs do not seem to completely explain the increasing mortality reported in the United States at a time characterized by reduced treatment time and dose. This raises the question of HD standard and adequacy. It stimulated us to analyze patient survival with unchanged 'old-times' methods. 445 unselected patients have been treated for 22 years by the same unchanged methods (24 m2/week, flat-plate dialyzers, cuprophane membrane, acetate buffer). Their survival data were compared to major HD registries and series. Survival was also evaluated as a function of mean arterial pressure (MAP), urea fractional clearance (Kt/V), and middle-molecule dialysis index (DI). Kaplan-Meier (with log-rank test) analysis and Cox proportional hazard model were used. Survival at short and long term was better in our series. This favorable survival difference was more obvious for older patients at the start of HD. It could not be accounted for by selection bias, but correlated with good MAP control without medication and with higher than usual Kt/V (1.67 +/- 0.41) and DI (1.47 +/- 0.38). Cox analysis including five covariates confirmed that survival was linked to MAP. It suggested that survival improvement might be expected from a DI increment of over 1.38 but not from a Kt/V increment of over 1.60. Adequate dialysis cannot be reduced to numbers; it should include both sufficient small- and middle-molecule diffusion and ultrafiltration with arterial pressure control without need for antihypertensive medication. The long-term satisfactory survival remains the best index of overall dialysis adequacy.


Hemodialysis 1991.

Hemodialysis remains the principal form of renal replacement therapy worldwide, and increasing numbers of patients have survived for 20 years or more. Future issues include the incorporation of newer technology into dialysis programs, ensuring adequacy of dialysis and optimum quality of care, controlling hypertension, and ensuring adequate nutrition. To maximize survival, hypertension must be controlled from its onset, smoking must be stopped, adequate dialysis provided, normal nutrition maintained, and blood access preserved. Home hemodialysis provides the best quality of life and opportunity for rehabilitation, but opportunities for this treatment may be limited. The long-term care of patients with end-stage renal disease requires careful attention to all aspects of their treatment on an ongoing basis, potentially for many years.


Shaded areas of CAPD.

It is well recognized that CAPD provides many advantageous points compared with hemodialysis as a kidney replacement therapy. However, there are a number of adverse facts which will result in withdrawal from CAPD. In this article, from my own experience on CAPD during the past 12 years, I deal only with shaded areas of this dialytic modality, such as the limitation of good candidates for CAPD, dysfunction of the peritoneal membrane, infectious complications, metabolic abnormalities and psychological stress. My conclusion is that CAPD is one of transient replacement therapies, although 'transient' may mean 5 or 6 years.


Anorexia and malnutrition in hemodialysis patients.

Malnutrition, which is common in maintenance hemodialysis (HD) patients, is strongly associated with increased morbidity and mortality. Protein requirements in HD patients are increased twice or more compared to those of healthy subjects. Underdialysis leads to anorexia with low protein and energy intake in relation to the requirements, resulting in protein and energy malnutrition, generally accepted recommendations for dialysis prescription regarding dose of dialysis and protein intake are probably inadequately low in relation to the requirements.


Induction of cytokines by dialysis membranes in normal whole blood: a new in vitro assay for evaluating membrane biocompatibility.

We investigated the capacity of cellulose cuprophane (CUP) and synthetic polyacrylonitrile dialysis membranes to induce the production of interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha using an in vitro model in which normal whole blood is incubated directly with calibrated membrane fragments. We found that only CUP membranes significantly increased plasma levels of IL-1, IL-6, and tumor necrosis factor alpha. The participation of lipopolysaccharide was excluded, since its addition to whole blood incubated with CUP led to a synergistic enhancement of IL-1 production, while the addition of polymyxin B had no significant effect. Transfer experiments showed that CUP-pretreated plasma was able to induce cytokine production by autologous monocytes. Inactivation of complement components prior to pretreatment abolished this effect. The participation of complement activation was further revealed by a correlation between cytokine and C5a plasma levels. Lastly, incubation of isolated monocytes with CUP but not with polyacrylonitrile also induced cytokine production, although to a lesser degree. In conclusion, our simple in vitro model can be used to evaluate the biocompatibility of dialysis membranes directly by using whole blood with greater relevance to the in vivo situation than models based on isolated blood components.


Reappraisal of long-term renal replacement therapy. Renal transplantation: medical versus statistical approach.

The validity of the numerous statistical methods used for the assessment of the results achieved with renal transplantation performed for terminally uremic patients may be challenged by a medicalized approach of the patient's post transplantation course and outcome. This assumption has been applied to a population of 700 patients who received a grafted kidney in our unit between November 1972 and December 1990. Among 77 patients who had been followed up for 10-15 years after grafting, 75% had not suffered any serious related complication during the first decade after transplantation. In contrast, among the whole transplant population, transplantation entailed either a rapidly fatal issue due to an unpredictable and irreversible complication in 45 patients (6.4%), or a state of chronic illness with severely disabling complications in 150 others (21.5%). At present, the main cause of concern remains, however, the persistent long-term graft loss due to chronic rejection. Nevertheless, the advances and results achieved in the field of organ transplantation in recent years justifies the policy which privileges renal transplantation as the first-choice method of renal replacement therapy for every terminally uremic patient aged less than 60-65 years in whom careful workup does not reveal any clinical/psychological contraindication.


Macromolecule adsorption to hemodialysis membranes depends on molecular size.

Adsorption to hemodialysis membranes was studied by determining the binding kinetics of model macromolecules, polydisperse DEAE dextran (molecular radii 10-70 A), to an acrylonitrile-methallyl sulfonate copolymer membrane. Hemodialyzers were studied in a postdilution hemofiltration circuit where both blood path output and ultrafiltrate streams were returned to the reservoir. Changes in the reservoir concentration of and sieving coefficients for DEAE dextran were monitored over 24 h. Decreases (or increases) in reservoir concentration were assumed to result from adsorption to (or desorption from) the membrane. Small macromolecules adsorbed rapidly to the membrane but later desorbed. This rapid adsorption resulted in low initial sieving coefficients. Large macromolecules adsorbed slowly over the entire 24-hour study period. Additional experiments suggested that desorption of small macromolecules was due to displacement by large macromolecules. Adsorption and desorption of macromolecules to hemodialysis membranes are dynamic processes and depend on molecular size.


[Random breath alcohol screening? Comments on the decisions of the 30th German Traffic Legislation Workshop (29 to 31 January 1992 in Goslar)].

When breathalyser tests are used to detect whether a person in charge of a vehicle is incapable of activing due to the influence of alcohol. The difficulties which arise are not limited to the extent to which these modern methods are forensically sound but extend to the question whether it is legally permissible to implement random breathanalysing. It is doubtful whether a duty to take a breath test, as yet unrecognized by the law (cf. section 36 Abs. 5 StVO), would be in conformity with the constitution. According to the established case-law of the Constitutional Court nobody can be compelled to put himself in danger of incriminating himself under the criminal law by their own act (under the principle "nemo tenetur se ipsum accusare"), which in this case would be a hard and prolonged breath into a breathalyser. The author sets the strict legal limits within which random breathalysing may be enforced.


[Retrospective analysis of blood collection protocols and blood alcohol analysis (Hamburg 1988)].

9,361 blood sample protocols (7,264 traffic and 2,097 criminal offences) of 1988 have been recorded and evaluated by electronic data processing under various aspects at the Institute for Legal Medicine in Hamburg. Since 1987 a slight increase of total offences was observed with a slight increase of alcohol-related traffic delinquency. Other results of the study are: The quota of women and as well of young people does not show an increasing tendency in alcoholic offences. In most cases older offenders had higher blood alcohol concentrations. More than 50% of the traffic offenders had a blood alcohol concentration above 1.3%. Altogether, criminal offenders had higher blood alcohol concentrations than traffic offenders. According to the common drinking- and leisure behaviour most of the alcohol delicts happened at weekends around midnight. In more than 50% the main traffic delict was drunken driving discovered by police control. Main criminal offences were delicts of property, bodily harm and resistance to police actions. With regard to alcohol habitation a great number of criminal offenders declares constant alcohol consumption, especially a lot of young people (under the age of 20). The medical diagnosis mostly pointed to slight or medium degree of drunkenness.


[Comparison of breath and blood alcohol concentration from measurements in police work].

4.135 measurements of breath- and blood-alcohol concentration were performed by police in 1986 and 1987 using the Alcomat A 11 (wavelength 3.4 microns). Important conclusions from these measurements can be derived with regard to legal breath-alcohol limits. The parameter for judgement is the breath- to blood-alcohol concentration ratio. Extreme deviations which have to be considered as malfunctions were found only in 0.4% of all cases, despite of the fact that not all precautions for evidential measurements are fulfilled. The reasons for malfunction may result from faulty breath- or blood-alcohol determinations or may simply be errors of transfer. The frequency of relatively too high breath-alcohol values (e.g. by interfering substances) is nearly the same as of relatively too low values (e.g. by too small breath volume). It has to be considered that the requirements according to the expertise of the Federal Health Office for evidential breath-alcohol measurements are only fulfilled partly. Especially the influence of breath-temperature is disregarded although the influence on frequency distributions is important as the comparison with other measurements demonstrates. A further result shows that the frequency distribution of the breath- to blood-alcohol ratio does not depend on blood-alcohol values.


[Isopropanol and acetone level in serum after preoperative surface disinfection with antiseptics containing isopropanol].

After preoperative skin disinfection in pediatric surgery, serum levels of isopropanol up to 12.2 mg/l (MW 5.0 mg/l +/- 3.37, n = 26) were found. They result from a rapid and prolonged but uncharacteristic percutaneous resorption of the isopropanol-containing disinfectant. In about 50% of the cases, serum levels of acetone showed an increase up to 82 mg/l already before skin disinfection, presumably caused by preoperative starvation. After skin disinfection, raised acetone levels were found in 19 of 26 cases. As increased isopropanol and acetone levels are discussed as alcoholism markers, a falsification of congener analysis after skin disinfection, e.g. in cases of adult victims of accidents, has to be taken into consideration. Endogenous serum levels of methanol (0.87 mg/l +/- 0.49), ethanol (0.32 mg/l +/- 0.09), acetaldehyde (0.31 mg/l +/- 0.10) and others remained unaffected. Some uncharacteristic elevations of propanol-1 levels are caused by contaminated rubber caps.


[Experiences with congener analysis of beverages without congeners].

Many alcoholic beverages contain no forensically relevant concentrations of congeners. Despite this fact they can be subject of a congener analysis. Another applicability of congener analyses are cases in connection with a differentiation between the short- or longterm ingestion of beverages containing 1-propanol and iso-butanol as congeners (e.g. beer or wine).


Comparison of ethanol concentration in saliva and blood from police controlled persons.

The salivary ethanol concentration correlates very well with the serum level (r = 0.98) in samples which are obtained almost simultaneously from persons undergoing a traffic control. If ethanol was referred to the aqueous compartment the saliva/plasma ratio was about 0.85; this ratio was about 11% less than the theoretical one and remained constant over the entire concentration range applied. Saliva could be taken together with breath samples from traffic participants which are controlled for ethanol consumption. The advantage of saliva in favour of blood is that it can be obtained nearly simultaneously with the breath sample without the intervention of a physician and does not hurt the person under suspicion. Furthermore saliva is suited for the voluntary surveillance of former alcoholics who are willing to prove that they are able to live abstinently.


The vulnerability of the hippocampus to protective and destructive effects of glucocorticoids in relation to stress.

The pituitary-adrenal axis participates in the diurnal response of the organism to the environment and in its response to stress. Circulating glucocorticoid and mineralocorticoid hormones act on cells in the brain via Type I and Type II receptors, which operate at the level of gene regulation, and mediate various feedback effects of adrenal steroids on brain chemistry and structure, including the operation of second-messenger generating systems, levels of structural proteins of glial cells, and the death and survival of neurons. The hippocampus is prominent in these effects, and it also displays the highest level of Type I receptors of any brain region. New concepts point to a special role of the hippocampus, a nexus of cognition and emotion, in the feedback actions of adrenal steroids during the diurnal rhythm, and in response to stress. The hippocampus is, therefore, a prime target area for investigation of the events which accompany stress, and which may be related to the maladaptive state that results in depressive illness. Initial studies are described which investigate the effects of tianeptine on pituitary-adrenal function, hippocampal morphology and Type I and Type II receptor levels.


Neurochemical and pharmacological properties of tianeptine, a novel antidepressant.

Tianeptine is a tricyclic antidepressant with an unusual chemical structure (a long lateral chain grafted on to a substituted dibenzothiazepin nucleus), and with biochemical and animal-behavioural properties which are strikingly different from those of classical tricyclics. Unlike the latter, which decrease serotonin (5-HT) uptake, acute and chronic tianeptine treatment enhances 5-HT uptake in rat brain and in rat and human platelets ex vivo. In vivo, tianeptine potentiates the depletion of rat brain 5-HT by 4-methyl-alpha-ethyl metatyramine and increases rat hippocampal 5-HIAA; 5-HT uptake inhibitors (e.g. fluoxetine) have opposite effects. On iontophoretic injection into CA1 pyramidal cells, tianeptine shortens the period of neuronal hypoactivity caused by GABA or 5-HT, whereas other tricyclics prolong it, and it enhances attention, learning, and memory in laboratory animals, while classical tricyclics have opposite effects. However, the relationships between these effects of tianeptine in animal experiments and their relevance to clinical findings remain to be determined.


Long-term use of tianeptine in 380 depressed patients.

Tianeptine is a new tricyclic compound whose principal action is to increase the reuptake of serotonin. In a multicentre trial in which 380 depressed patients were treated for one year, tianeptine produced a significant reduction in the MADRS scores from day 14, with a sustained reduction maintained for up to 12 months; other measures of efficacy (HRSA, HSCL, and CGI) also reflected the improvement. Only 11% of patients withdrew because of recurrence of depression and 2% because of side-effects, which were mainly drowsiness, irritability, and gastrointestinal disturbance. Apart from a minor reduction in heart rate, unaccompanied by any conduction changes, no clinically relevant changes in vital signs or laboratory tests were seen. Seven subjects who attempted suicide by tianeptine overdose had favourable outcomes, in spite of also taking other psychotropic drugs or alcohol. No evidence of tolerance or withdrawal symptoms was seen after treatment was stopped. These results suggest that tianeptine has the potential to provide safe antidepressant activity in both the acute and chronic phases of treatment.


Long-term administration of tianeptine in depressed patients after alcohol withdrawal.

Alcohol interferes with the central metabolism of the catecholamines and especially with indolamines (5-HT). Thus, the use of an antidepressant such as tianeptine, whose main neurochemical effect is to increase the reuptake of 5-HT, seems to be particularly indicated for the continued treatment of depressed patients after alcohol withdrawal. This study evaluated the therapeutic efficacy and acceptability during long-term administration of tianeptine in depressed patients (major depressive episode or dysthymic disorder) in a multicentre trial, after withdrawal from alcohol abuse or dependence. The results relate to 130 depressed patients, who abstained from alcohol and received treatment for a year. Only one patient dropped-out because of side-effects, and medication was interrupted in 5% of subjects because of alcoholic relapses. Prescribed in the long term, tianeptine did not produce orthostatic hypotension, changes in bodyweight, or alterations in the ECG. All changes found in haematological and biochemical investigations suggested an improvement in patients' physical state. This, and other studies, indicate that tianeptine appears to have the potential to be a safe antidepressant, which might be particularly useful in those patients who are susceptible to the side-effects of psychotropic drugs.


Efficacy of tianeptine in comparative trials versus reference antidepressants. An overview.

The clinical properties of tianeptine have been assessed in double-blind controlled studies, which involved depressed patients fulfilling DSM-III criteria for either major depression--single episode or recurrent (without melancholia and psychotic features)--or dysthymic disorder--with or without an additional diagnosis of alcohol abuse or dependence. Five studies have compared tianeptine with reference antidepressants: its efficacy has been found to be similar to that of amitriptyline in depressed out-patients. However, these data need to be confirmed by other controlled trials v. reference drugs and by at least two placebo-controlled studies. Tianeptine does not induce sleep disorders, anticholinergic effects, or modifications of cardiovascular variables or biological parameters (renal, haematological, or hepatic). After the end of treatment, the only signs of withdrawal have been some disturbances of sleep.


Relationship between the neuroses and brief reactive psychosis: descriptive case studies in Africa.

Predominant psychopathology in a selected population group--adolescents and young adults at school--in a developing country, is described. The highly selective referral to services was supplemented by active case finding in the community over three years. There were 54 cases of somaticised anxiety (brain fag); 22 cases of depressive neurosis characterised by hypochondriasis, cognitive complaints, and culturally determined paranoid ideation; 23 cases of 'hysteria' in the form of dissociative states, pseudoseizures and fugues; and 39 cases of brief reactive psychosis which differed from the dissociative states more in duration and intensity than in form. There was a temporal relationship between transient psychosis and the school calendar. Anxiety or depression often predated the florid psychotic reaction which served as a form of help-seeking behaviour or defence in intolerable stress.


Brief reactive psychosis and the major functional psychoses: descriptive case studies in Africa.

In a three-year prospective study of service-based incidence of functional psychoses in Africa, 94 cases of brief reactive psychosis were compared with 56 cases of schizophreniform syndromes, 29 cases of DSM-III schizophrenia and 14 of manic-depressive psychosis. This was supplemented by retrospective study of the same syndromes not in their first episode. Brief reactive psychosis was found to be a composite syndrome. The 50% with preceding depression were a distinct group, in terms of course and demographic features. Of those with intense prodromal anxiety, most were a single episode precipitated by a major life event, a few showed a recurrent long-term pattern. Schizophrenia was heralded, or presented unequivocally months or years later, in 10-20%. The schizophreniform group comprised a range of atypical psychoses intermediate between the transient and major psychoses. The pattern of precipitants and the over-representation of education and paid employment in the acute syndromes, compared with the major psychoses, in a society which was largely first-generation educated, suggested a link with rapid social change.


Profile and prevalence of the brain fag syndrome: psychiatric morbidity in school populations in Africa.

The profile and prevalence of a syndrome of somaticised anxiety associated with education in Africa was explored by survey of 2040 senior secondary school students in different types of school: rural, urban, and elite. Response to two different screening methods, an open question to elicit symptoms spontaneously, and the SRQ-24, was compared. Symptom prevalence was higher in rural schools, 34%, than periurban, 22%, and elite, 6%, but the central urban school serving a shanty town was also high at 35%. Three categories of the culturally relevant symptoms were identified--somatic, cognitive and 'spiritual'--with affective symptoms sparsely represented in the cultural idiom. The SRQ-24 items screening for psychosis were associated with a range of spontaneous symptoms representing anxiety. This 'spiritual' expression of neurosis reflects the world views and beliefs of the culture. Intensification under stress could produce the picture of transient reactive psychosis.


Social origins of the brain fag syndrome.

The aetiology of psychiatric morbidity associated with education in Africa was explored using two different screening methods (as described in paper III, this supplement). The interactive effect of psychosocial variables was examined by Log linear analysis which demonstrated five independent factors: (a) the financial implications of education which represented the change from subsistence to cash economy; (b) fear of envy and bewitchment which represented the intense cultural response to education; (c) parenting in the pre-school years which was the independent family variable; (d) academic ability; (e) attributes of the school. Age of starting school and birth rank had a marginal effect. Current family adversity in terms of unstable parental union, paternal use of alcohol, polygamy and sibship size operated by interactive or additive effect. Gender and social status had no effect. The brain fag syndrome can be related to the complex social changes during rapid social transition where education is a major agent of change.


Four-quadrant cricoid cartilage division in laryngotracheal reconstruction.

Four-quadrant division of the cricoid cartilage is a relatively new technique of laryngotracheal reconstruction. Division of the lateral walls of the cricoid cartilage, with or without placement of autogenous cartilage grafts, allows for increased expansion of the subglottic lumen. Between October 1, 1986, and January 1, 1990, 185 laryngotracheal reconstructions were performed at our institution. During that time, 31 four-quadrant division laryngotracheal reconstruction procedures were performed in 29 patients (mean age at surgery, 5 years 5 months). Grade 3 or 4 laryngeal stenosis existed preoperatively in 72% (22/31) of cases. The initial decannulation rate after four-quadrant division laryngotracheal reconstruction was 58% (18/31). Of 11 patients requiring revision surgery after four-quadrant division laryngotracheal reconstruction, four were eventually decannulated, for an overall decannulation rate of 76% (22/29). The indications, technique, results, and potential complications of four-quadrant division of the cricoid cartilage in laryngotracheal reconstruction are discussed.


Gastropharyngeal reflux in infants and children. A pharyngeal pH monitoring study.

Gastroesophageal reflux has been shown to play an important role in chronic and acute inflammatory disorders of the airway. In particular, gastroesophageal reflux has been suggested to be the cause of pharyngolaryngeal problems, according to the literature, at any age. However, to our knowledge, the presence of acid in the pharynx in pathological cases has not yet been proved. A series of eight patients (aged 2 months to 7.5 years) with recurrent acute laryngotracheitis underwent a two-channel pH monitoring for 23 to 24 hours. One pH probe was placed in the lower esophagus, the other in the pharynx, at the level of the epiglottis. Acid gastroesophagopharyngeal reflux was demonstrated in every patient. A significant difference with a series of six control subjects was noted in terms of esophageal and pharyngeal pH monitoring. The most significant item is the total time the pH in the pharynx was below 6. Despite the limited number of patients, this study suggests the role of gastroesophageal reflux in recurrent laryngotracheitis in infants and children.


Chemosensitivity and DNA ploidy in head and neck squamous cell carcinomas.

The succinate dehydrogenase activity and cellular DNA content of human head and neck squamous cell carcinomas were examined, and the chemosensitivity and ploidy status were compared with histologic differentiation. The average decrease of enzyme activity in the poorly differentiated squamous cell carcinomas was significantly greater than that of well- and moderately differentiated squamous cell carcinomas. Statistically significant differences were also noted with relation to the original site of the primary tumor. The chemosensitivity of a tumor with DNA aneuploidy tended to be lower among the well- and moderately differentiated squamous cell carcinomas and higher among the poorly differentiated type. We conclude from this study that simultaneous analysis of the chemosensitivity and DNA ploidy will aid not only in selecting effective antitumor drugs but also in predicting changes in cellular characteristics during the course of disease.


Postoperative radiation-associated changes in free jejunal autografts.

Free jejunal autografts are a preferred method of pharyngoesophageal reconstruction. Ten adult mongrel dogs underwent free jejunal transplantations to the neck, five being controls and five receiving a 55-Gy equivalent dose of radiation after 3 weeks. Histologic changes 10 months after radiotherapy included simplified and blunted villi with normal architecture loss; fibrous replacement of the lymphatics and microvasculature in the intravillous space; goblet cell increase; significant increase in lamina propria thickness and muscularis mucosa fibrous plates; focal destruction and replacement of muscle layers with fibrosis; gross hypertrophy of the myenteric plexus with increased fibrous tissue about the hypertrophied neural tissue; and significant perivascular fibrosis. Controls demonstrated only minimal changes. These adverse delayed effects of irradiation on revascularized jejunal autografts should be considered in planning the method of pharyngoesophageal reconstruction as well as timing of adjuvant radiotherapy.


Monitoring of revascularized jejunal autografts.

Free jejunal autografts have been widely used to reconstruct circumferential pharyngeal defects in a single stage. Close postoperative monitoring of the perfusion of the free jejunal autograft is extremely important in achieving a successful outcome. Presented herein is our method of postoperative monitoring of jejunal autografts in which a segment of jejunum pedicled on its connecting mesentery is exteriorized. This method of monitoring was performed in 17 cases, and there were no cases of late graft failure. Of three patients who had undergone this operation before the use of this monitoring technique, one had an unrecognized late graft failure. We present our experience with this simple and reliable method to monitor free jejunal autografts.


Head and neck liposarcoma. A histopathologic reevaluation of reported cases.

Head and neck liposarcoma is an extremely rare tumor. As with all rare lesions there is a void in the literature regarding tumor activity and treatment response. It is difficult to make rational treatment plans and advise patients as to probable treatment response and prognosis. To obtain as much information as possible from available data we have reviewed the world literature and reevaluated the descriptive histopathologic findings and treatment response of reported cases. Seventy-six cases have been reported since 1911. We added another case and then reclassified the previously reported lesions according to a current histopathologic system (well-differentiated, myxoid, round-cell, and pleomorphic lesions). We assessed tumor activity and treatment response by histopathologic tumor type. Paralleling tumor activity in other anatomic regions, all patients with myxoid and well-differentiated tumors did well; all were alive at the end of follow-up, eight of eight and 11 of 11, respectively (average follow-up, 5.7 and 4.8 years). This is compared with a 50% mortality rate in the round-cell and pleomorphic groups by the end of 2 years, (two of three and six of 11 patients alive, respectively). The likelihood of recurrence correlated with extent of tumor removal, and metastatic disease was identified almost exclusively with the tumor of the round-cell and pleomorphic variants. Surgical excision remains the primary treatment modality, while radiation and chemotherapy appear to be of limited utility.


The influence of intensive hyperbaric oxygen therapy on skin flap survival in a swine model.

Conflicting reports exist regarding the influence of hyperbaric oxygen therapy on random skin flap survival. The present investigation sought to demonstrate enhanced survival of experimental random skin flaps in swine using an intensive and tapering hyperbaric oxygen therapy regimen that would have direct application in human clinical trials. Random cutaneous flaps were surgically constructed on 12 domestic pigs. Flaps were designed to obtain a predictable length of necrosis. Six pigs did not undergo hyperbaric oxygen therapy and served as surgical controls. Six pigs were subjected to an intensive tapering hyperbaric regimen within 1.5 hours of completing the surgical procedure. Treatments were administered in a research hyperbaric vessel at a depth of 2.0 atm absolute (10 m of seawater) for 90 minutes of oxygen treatment in a tapering schedule over 6 days. This was structured to provide intensive therapy initially during the period of maximum tissue trauma and ischemia. Extent of flap necrosis was assessed by tracing clear plastic templates at necropsy, then converting to square centimeters using a computer digitizer tablet. The difference in flap necrosis between groups was significant, with random flaps subjected to hyperbaric oxygen therapy demonstrating a mean 35% less necrosis than surgical controls. Skin flaps treated with hyperbaric oxygen therapy demonstrated a mean survival of 77%, with a range of 56% to 100%. This reflected a 12% improvement in mean surviving area for hyperbaric oxygen therapy flaps over untreated surgical controls. We are unaware of similar studies reporting a comparable degree of enhancement in random skin flap survival using hyperbaric oxygen therapy alone. Adjunctive hyperbaric oxygen therapy in an intensive tapering schedule significantly improved flap survival in this model. Further investigations need to determine the optimum frequency of treatments and depth necessary to attain maximum tissue viability.


Middle fossa vestibular neurectomy in retrolabyrinthine neurectomy failures.

Retrolabyrinthine vestibular nerve section is an important treatment option in patients with refractory, incapacitating vertigo. However, an indistinct cleavage plane between the cochlear and vestibular portions of the eighth cranial nerve may result in incomplete sectioning of the superior and inferior vestibular nerve fibers. We describe 11 patients in whom middle fossa vestibular neurectomy was performed following failure of a retrolabyrinthine vestibular neurectomy. A successful postoperative outcome from this revision surgery was obtained in six of 11 patients on follow-up evaluation. Patients in whom infrared video electronystagmography showed persistent function of the inferior vestibular nerve following retrolabyrinthine vestibular nerve section had a better response to middle fossa vestibular neurectomy than those with no measurable residual vestibular function. Because it provides access to the vestibular nerves where there is separation from the cochlear nerves distal to the previous section, we feel that the middle fossa vestibular neurectomy is the procedure of choice in selected patients who fail retrolabyrinthine neurectomy.


Some aspects of life quality after surgery for acoustic neuroma.

This investigation was performed to describe some aspects of the quality of life in subjects after translabyrinthine removal of an acoustic neuroma, resulting in unilateral total deafness. Two hundred ninety-three subjects who had been operated on during 1976 through 1990 and who were living outside the Copenhagen (Denmark) City and County received a postal questionnaire, to which 93% (n = 273) responded: 118 men and 155 women with a median age of 58 years (range, 18 to 81 years). The median observation period from surgery to the questionnaire was 6 years (range, 6 months to 14 years), and the median age at operation was 52 years (range, 15 to 76 years). Among the subjects, 22% had received postoperative hearing rehabilitation with various types of hearing aids in the ear not operated on. In 62%, tinnitus was experienced in the ear with tumor before surgery, and at the time of the questionnaire, 49% experienced tinnitus in the ear operated on. Half a year after surgery, 56% still experienced dizziness. Sixty-four percent reported damage to the facial nerve in relationship to the operation. At the time of the questionnaire, 12% indicated a total loss of facial nerve function. No vocational consequences were found in 74% after surgery. Information concerning different symptoms related to surgery was insufficient in 29%, while the quality of information in relation to surgery was more satisfying. In conclusion, the study demonstrates that deafness, dysequilibrium, and reduced facial nerve function caused the most severe problems. Improved information to patients before surgery may reduce the frequency of negative experiences.


Distortion-product otoacoustic emissions. Values for clinical use.

Distortion-product otoacoustic emissions are otoacoustic emissions evoked by two pure tones. They are proposed as a frequency-specific test of the mechanical properties of the cochlea. The aim of this study was to measure distortion-product otoacoustic emissions in a clinical setting to establish the most interesting values suitable for clinical use and the clinical interest of the method. The statistical analysis of the data points out some clinically interesting values: (1) a screening limit value of 30 dB hearing level and when measuring distortion-product otoacoustic emissions in response to 52 dB sound pressure level for studying active frequency selective mechanisms; (2) a screening limit value of 50 dB hearing level and when measuring distortion-product otoacoustic emissions in response to 72 dB sound pressure level for studying passive cochlear mechanisms; and (3) the slope of the input-output function. All physiologic properties of the cochlea fit with these basic distortion-product otoacoustic emission properties. These criteria can be used whatever the population studied and the material used for distortion-product otoacoustic emissions recordings. Distortion-product otoacoustic emissions can be used as a screening test to separate (1) subjects with normal hearing and subjects with a hearing threshold above 30 dB hearing level (distortion-product otoacoustic emissions in response to a 52 dB sound pressure level "primaries" [ie, pure tones] stimulation intensity), and (2) patients with a hearing threshold above or below 50 dB hearing level (distortion-product otoacoustic emissions in response to a 72 dB sound pressure level primary stimulation intensity). Distortion-product otoacoustic emissions cannot be used as a more precise audiometric test.


Three-component analysis of caloric nystagmus in humans.

Three-component analysis of caloric nystagmus, focusing on the horizontal, vertical, and torsional, using a computerized eye movement analysis system, was carried out in 10 normal human subjects. The caloric response was induced by cold stimulation to the right ear of the subjects in the supine and prone positions. In the supine position, the three components of nystagmus were toward the left (10 subjects), upward (eight subjects) or downward (two subjects), and clockwise (10 subjects). In the prone position, on the other hand, the three components were directed toward the right (10 subjects), downward (five subjects), upward (three subjects), and counterclockwise (10 subjects); there was no vertical direction in two subjects. These findings indicate that caloric stimulation activates the three semicircular canals simultaneously. Also the changes in the nystagmus direction in the supine and prone positions could be explained, at least partially, by the nonconvective component of caloric stimulation.


Lateral arm free flap in head and neck reconstruction.

The lateral arm fasciocutaneous free flap is a versatile donor site of sensate soft tissue for reconstruction and augmentation of the head and neck. The lateral arm flap can be quickly harvested without interference to the head and neck team and with minimal morbidity to the patient. For these reasons, this flap has become our soft-tissue flap of choice.


Extended access/internal approaches for the management of facial trauma.

The two most significant recent developments in the treatment of facial trauma are the introduction of plating systems, which provide rigid internal fixation and the development of surgical approaches that allow wide exposure of the entire facial skeleton while minimizing external incisions. These approaches (referred to as extended access/internal approaches) are hemicoronal and coronal flaps, the sublabial approach to the midface, the transconjunctival approach to the orbital floor and orbital rim, and the intraoral management of mandibular fractures. These approaches work well, and have become standard techniques for managing facial trauma; however, each one has definite technical points that need to be adhered to to assure their success. Additionally, there are situations where these approaches are not appropriate and, in fact, may even be detrimental. This article outlines our approach to facial trauma using these extended access/internal approaches and discusses the important technical factors of each approach. Our experience in treating 113 patients with 119 fractures and 161 approaches over the last 2 years is presented and the role extended access/internal approaches have played is reviewed. The indications, limitations, and possible complications associated with each approach are outlined.


Hiccups. A case presentation and etiologic review.

Hiccups (singultus) usually present as a common annoyance lasting for short periods. Rarely, they may be the harbinger of a serious disease. We present the case of a 19-year-old man in which intractable hiccups was the first and most prominent symptom of a serious underlying neurologic disorder. The patient had been examined by his pediatrician, and despite multiple medical regiments and physical maneuvers, his symptoms persisted. A thorough head and neck examination revealed a right-sided vocal cord paralysis. This finding prompted obtaining a magnetic resonance imaging scan, which demonstrated a type I Arnold-Chiari malformation associated with a large cervicothoracic syringomyelia. The patient was referred to the neurosurgical service and subsequently underwent a ventriculoperitoneal shunt placement. There was considerable initial improvement in his neurologic status and cessation of the hiccups. However, the symptoms recurred within 1 month. The case report as well as a brief review of the relevant pathophysiologic and etiologic considerations and several treatment modalities for hiccups is presented.


Autoantibodies against constituents of neutrophils in the diagnosis and treatment of (isolated) subglottic stenosis.

Six patients had a subglottic stenosis either as a presenting symptom or as a manifestation of a systemic disease. All patients had in common the presence of circulating autoantibodies against constituents of neutrophils on indirect immunofluorescence. Cytoplasmic and perinuclear staining patterns were recognized. Such autoantibodies have been reported in Wegener's granulomatosis, microscopic polyarteritis, (idiopathic) glomerulonephritis, and Churg-Strauss syndrome. However, only one of the six patients fulfilled the criteria for these conditions. Because a positive test for autoantibodies against constituents of neutrophils is rare in other conditions and because other diseases had been excluded, we suggest that this places subglottic stenosis within the spectrum of necrotizing (granulomatous) vasculitis. The consequences for therapy are discussed.


Magnetic resonance imaging of the large vestibular aqueduct.

The large vestibular aqueduct syndrome describes an abnormally large endolymphatic duct and sac with associated sensorineural hearing loss. This entity was originally reported in 1978 and has since been identified as a finding in children with progressive hearing loss. The original description of the large vestibular aqueduct employed hypocycloidal polytomography of temporal bone. Subsequent reports studied patients identified with this syndrome using computed tomographic scans. We report magnetic resonance imaging of two patients diagnosed with the large vestibular aqueduct syndrome. The magnetic resonance imaging and computed tomographic scans are compared and the significant findings on magnetic resonance imaging are reviewed. This should assist the otolaryngologist and radiologist with establishing the appropriate diagnosis.


[Effect of various heavy metals on the ATP content of spermatozoa from Arbacia lixula L.--activity of mercury].

This work reports the evaluation of some toxic effects induced by mercury on sea urchin sperm. Spermatozoa of the sea urchin Arbacia lixula L., were treated with 0.003, 0.03 and 0.06 mg/l of Hg. We estimated the amount of ATP of sperm cells with the luciferin-luciferase reaction, and we also observed motility, fertilizing activity and number of sperm bound to the eggs. The results clearly show that ATP levels are strongly affected by mercury concentrations, already three hours after the beginning of treatment. We propose the use of ATP determination in sea urchin sperm as a bioassay, because they, even more than eggs and developmental stages, readily suffer the environmental stresses.


Functional properties of dilute Hb solutions studied without tonometric techniques.

The authors found that, by continuously bubbling pure nitrogen within a dilute Hb solution, the latter releases its oxygen with an intensity which is quite proportional to the duration of bubbling. Such a procedure can be employed instead of the common tonometric technique, to measure functional properties of Hb. In fact, not only dissociation curves can be obtained, but also a correct evaluation of the affinity changes upon pH variations (Bohr effect). The results obtained by this technique are not far from those recently reported by using tonometry, although the method is less precise and still not suitable for routine purposes. Nevertheless, it can be substantially improved.


Functional behaviour of dilute solutions of Hb-Kempsey: beta 99 (G-1) Asp--Asn.

The authors report that a diluted solution of Hb-Kempsey, beta 99 (G-1) Asp-Asn, can be chromatographically separated from the coexistent Hb-A and functionally examined if progressively depleted in O2 by bubbling pure nitrogen in the solution. Next, at fixed times, the O2 saturations of Hb are compared with the pO2s measured. Hb-Kempsey has a p50 of 1 torr, with an n-value of 1 and a Bohr effect of -0.2. Normal Hb-A of the same patient, examined with identical methods, presents: p50 = 4.5 torr; n = 2.7; Bohr effect = -0.412. Therefore, Hb-Kempsey is strongly hyperaffinic, does not display any heme-heme interaction, and has a half-normal Bohr effect.


[Correlation of the clinical phenotype with a pericentric inversion of chromosome 9].

Pericentric inversion of chromosome 9 is one of the most common structural balanced chromosomal aberrations. It is considered as a paraphysiological variant of a normal karyotype and it is possible to find it as occasional report in healthy subjects. In the last ten years different signals have appeared in literature, concerning carriers of pericentric inversion of chromosome 9, who showed different anomalies of the clinical condition. Today it is difficult, because of the rarity of the data to establish if a true correlation exists between phenotypical anomalies in the subjects studied and the pericentric inversion, or if they are only casual associations. We are trying to find possible correlations between the chromosomal rearrangements and eventual congenital defects. We describe 11 subjects with pericentric inversion of chromosome 9 examined for the presence of dysmorphic signs, mental retardation and repeated miscarriage.


[Familial segregation of simple and complex chromosomal rearrangements].

We report our observations about familial segregations of chromosomal aberrations: the simple forms and complex rearrangements. Congenital malformations and mental retardation, can be present both in unbalanced and in balanced translocations. Various hypotheses have been proposed to explain this phenomenon: in particular a possible "position effect" or genic mutation or genomic imprinting. In our study we have used both standard techniques and techniques with high resolution banding to investigate if the rearrangements were balanced or not. Molecular study and gene dosage have been used when possible, to define the correlation with the clinic phenotype.


Silent cholinesterase gene: three homozygotes in a small Caucasian population.

Three sera, showing only a 2-3% of the usual cholinesterase activity and belonging to two families of 800 Caucasian inhabitants of the same small town, were classified as type II silent cholinesterase genes by polyacrylamide slab gel electrophoresis, dibucaine and fluoride number and by their specific activity with acetyl- butyryl- or propionyl-thiocholine.


[Interaction between vision and vestibular nystagmus].

In order to assess the visuo-vestibular interaction and its behaviour in connection with the age, we have submitted 20 healthy subjects from two age groups ranging between 21-30 and 65-75 years of age to two rotation tests (with closed eyes and with opened eyes with fixation of a light). The results show a variation of the nystagmic response with fixation of about 60% in the young people and of about 40% in the elderly. These results demonstrate that the extent of the inhibition is dependent upon age and is less effective in the elderly.


[Brain-stem auditory pathways: effects of atropine].

The efferent pathways exert a control action on the function of the cochlear nucleus and hair cells. Acetylcholine is the neurotransmitter of the centrifugal system and its action can be blocked by Atropine. In order to give a contribution to the knowledge of the function of the efferent bundle, Auditory Brainstem Responses (ABRs) and Acoustic Reflex Latencies (ARLs) have been examined in 10 young normal subjects there was also a decrease in latency greater than or equal to 100 microseconds by at least other two waves. The only statistically significant difference was relative to the latency mean value of the wave III recorded in contralateral derivation at 11 pps. The ARLs, after the infusion of atropine, showed a statistically significant increase in 7 of the 10 cases; no change was recorded in the AR amplitude. It can be concluded that the pharmacological block of the olivo-cochlear bundle determines a delay in the neural conduction of the acoustic impulses; this finding means that the atropine can inhibit the facilitating activity of the efferent system on the brainstem afferent pathways.


[Evoked acoustic oto-emissions in cochlear deafness].

In order to give a contribution to the genesis of the EOAEs, we have recorded echos in 24 subjects with unilateral sudden deafness (I. group); 20 ears with Menière disease (II. group); 22 ears with progressive sensorineural hearing loss (III. group) and 10 normally hearing young subjects as control group. The results have shown that the EOAEs were present in 100% (I. group), 84.6% (II. group) and 86.3% (III. group) in response to the tone-burst; while the echos were present only in the 57.1% (I. group), 38.4% (II. group) and 45.4% (III. group) in response to the click, although the audiometric threshold mean were greater than 45 dB HL for 2-4 KHz and 1 KHz in the three experimental groups except for 2-4 KHz in the subjects with Menière disease (37.5 dB HL). The properties of EOAEs (detection and saturation threshold, dynamic range and duration) depended on the degree of hearing loss. Our results seem to corroborate the hypothesis that EOAEs could be also produced by a passive intracochlear mechanism attributable to the travelling wave of the basilar membrane provoked by the perilymph. In the normal ear this passive mechanism could be superimposed by an active mechanism, linked to the contractile activity of the outer hair cells with a consequent increase in amplitude of the EOAEs for the same stimulus intensity.


Alzheimer disease brain extract stimulates branching of laminin-mediated neuronal processes.

Patients with Alzheimer disease (AD) suffer mental deterioration associated with neurofibrillary tangle and senile plaque formation in the brain. Here we have determined the effects of brain extracts from normal and from AD patients on neuronal process formation by a pheochromocytoma (PC-12) and a neuroblastoma x glioma hybrid cell line (NG108-15). PC12 cells show a dose-related stimulation of branching of neuronal processes by AD brain extracts with cells cultured on a laminin substrate. The neurotrophic effects of extracts of AD brains may be related to the abnormal sprouting and neurofibrillary tangle formation observed in the brain in this disorder.


DSM-III-R criteria for primary degenerative dementia and multi-infarct dementia [corrected].

Primary degenerative dementia (PDD) and multi-infarct dementia (MID) are the two most common categories of cognitive decline in old age. The definitions of these two clinical entities are currently based on clinical evaluation and on the exclusion of other underlying causes, and still lack a consensus. The DSM-III-R criteria are widely used for the diagnosis of dementia. However, their role in the differentiation between PDD and MID has not been thoroughly examined. A consecutive series of 98 demented patients who met the DSM-III-R criteria for dementia were admitted to a clinical study. Upon evaluating their type of dementia according to these criteria, 53 patients could not be diagnosed either as having PDD or MID. The DSM-III-R criteria for these two types of dementia are critically reviewed. Proposed modifications, aimed at refining their differential diagnostic role, are presented, enabling better allocation of demented patients into PDD, MID, or intermediate groups.


Management of behavior disturbance in Alzheimer disease: current knowledge and future directions.

Assessment and treatment of behavior problems in patients with Alzheimer disease and related disorders is a seriously neglected area of study. Despite the fact that such problems are integral to the disorder, little is known about effective management. This article summarizes the current thinking on five areas of prime importance to patients, care providers, and health care professionals: agitation, assault/aggression, screaming, wandering, and depression/apathy/withdrawal. Methodological guidelines for studying these disorders are provided. Emphasis is on recognizing that behavior problems are important areas of study in their own right as well as in conjunction with studies of cognition.


Alzheimer disease assessment scale: useful for both early detection and staging of dementia of the Alzheimer type.

The Alzheimer Disease Assessment Scale (ADAS) was administered to 61 patients with dementia of the Alzheimer type (DAT) and 52 elderly controls. The DAT group was subdivided into different severity levels of dementia based on scores from the Mini-Mental State Exam: very mild (greater than or equal to 24), mild (20 to 23), moderate (10 to 19), and severe (0 to 9). The mean scores on the ADAS Cognitive subscale for the four levels of dementia (very mild = 23.1 +/- 7.7, mild = 22.9 +/- 8.9, moderate = 38.6 +/- 9.8, severe = 54.8 +/- 7.6) were statistically different from one another (p less than 0.0001, except very mild vs. mild) and were significantly worse than the scores of the elderly control group (5.5 +/- 2.7, p less than 0.0001, ANOVA). Furthermore, the ADAS Cognitive subscale was highly effective in discriminating individual Alzheimer patients from elderly controls. The ADAS Cognitive score correctly classified 100% of the very mild group, 91% of the entire mild group, and 100% of the moderate and severe groups when a cutoff score of 2 SDs above the control group mean was used. Age and education had only minimal effects on the ADAS Cognitive score. The ADAS is a valuable screening test that only takes 30 min to administer and has utility in both early detection and staging of DAT.


Evaluation of growth hormone secretion and treatment.

The secretion of growth hormone (GH) is regulated by a complex system that includes both neurotransmitters and feedback by hormonal and metabolic substrates. Over the last few years it has been recognized that GH release varies over a wide spectrum from deficient to excessive secretion. The diagnosis of GH deficiency is based on a combination of anthropometric and clinical signs on the one hand and an inadequate stimulated and/or spontaneous GH secretion on the other. There is no distinct boundary between deficient and sufficient GH secretion. The cut-off limit for normal GH release is accordingly relative and has increased over the past decade from 5 to 10 micrograms/l. The effect of GH therapy on growth can be evaluated only after treatment for at least 6 months. There is, therefore, an indisputable need for methods that would reflect growth response soon after the start of treatment. There are several promising biochemical candidates, e.g. the aminoterminal propeptide of type III procollagen, the carboxyterminal propeptide of procollagen I and the bone Gla-protein, which may turn out to be useful early indicators of the growth response to long-term GH therapy.


Emerging role of heat shock proteins in biology and medicine.

All cells, procaryotic and eucaryotic, respond to an elevation in temperature by increasing the synthesis of a family of proteins collectively known as heat shock proteins (HSPs). HSPs are among the most highly conserved and abundant proteins in nature. Studies on the regulation of the synthesis of HSPs have for several years shed light on the mechanisms regulating gene expression. The results from recent years, showing that HSPs play crucial roles in a wide variety of normal cellular processes, has made them an object of even broader interest, first to molecular and cellular biologists and later to specialists in various fields of medicine including oncology, immunology, infectious disease, autoimmunity, embryology, neurology and endocrinology. The aim of this review is to briefly summarize our present knowledge of the regulation of the heat shock response and the structure of the relevant gene products, HSPs. Moreover, some of the exciting associations between HSPs and various fields of medicine will be discussed.


Male infertility: current concepts.

The purpose of the article is to review the current concepts regarding the etiology and treatment of male-factor infertility. The following general conclusions can be drawn: (a) conventional parameters for sperm quality and male fertility are inadequate and any assessment should involve several different tests of sperm cell function to increase the fertility prognosis; (b) the causes of disturbed sperm quality are still poorly understood; (c) the role of the varicocele is still controversial but some of the discrepancies reported in the literature may be explained by the negative influence of other factors such as smoking, epididymal pathology or glandular infections operating either in conjunction or independent of the varicocele; (d) the role of chronic inflammatory processes in the reproductive organs, in particular the involvement of chronic chlamydial infections, has been underestimated, largely because it is often asymptomatic and difficult to demonstrate objectively; (e) partial androgen insensitivity may account for a significant number of cases of severe oligozoospermia; (f) no major advances have been made in the medical treatment of poor sperm quality; (g) assisted fertilization techniques such as IVF and GIFT offer encouraging possibilities for the treatment of male-factor infertility; and (h) recent advances in microsurgical techniques are increasing the treatment possibilities for certain forms of obstructive azoospermia and severe oligozoospermia.


Transgenic animals as bioproducers of therapeutic proteins.

Many human therapeutic proteins are currently produced with the aid of recombinant DNA technology in microbial bioreactors and a few also in large-scale animal cell cultures. Although extremely cost-efficient, the microbial production system has many inherent limitations. Micro-organisms, such as bacteria, can read the universal genetic code and hence produce human proteins with correct amino acid sequence, but cannot carry out post-translational modifications, such as glycosylation, or fold the newly synthesized protein properly to ultimately generate a biologically active entity. Moreover, even though the production of the proteins as such is inexpensive, the downstream processing of the final product may be extremely difficult and costly. Many of these disadvantages, especially the lack of post-translational modifications, can be overcome by employing large-scale animal cell cultures for the production of proteins of pharmaceutical interest. However, due to the long generation time and the requirement for rich culture media, the use of animal cell bioreactors is unacceptably expensive. With the advent of transgenic technology, the production of human pharmaceuticals in large transgenic animals has become more and more attractive. The use of targeted gene transfer, the expression of the transgene of interest can be directed to occur in the mammary gland of large farm animals, such as pigs, sheep, goats or dairy cattle, and hence the transgene product is ultimately being secreted into the milk. Although not yet in commercial use, the last few years have witnessed a remarkable progress in this area and proved the feasibility of the use of 'molecular farming' in high-quantity, low-cost production of valuable therapeutic or industrial proteins. While reviewing the progress of the field over the past few years, we discuss in somewhat greater detail aspects connected with the use of dairy cattle as bioproducers of human therapeutic proteins.


Eating disorders: antecedents, evolution and course.

Concepts of eating disorders have altered so that anorexia nervosa is now recognized as an important but uncommon syndrome within a spectrum of disordered eating. Behaviours used by dieters constitute the mild end of the eating disorder spectrum. Dieting in young women is for the most part a transient and benign activity without longer-term consequences. However, a group of dieters do progress to develop the symptoms and behaviour of eating disorders, so that dieting has been associated with an eight-fold rise in the risk of later eating disorder. Dieting or factors closely associated may account for most eating disorders in young women. Many antecedents of eating disorder appear to operate through increasing the risk of dieting rather than determining eating disorders specifically. Only the development of further neurotic and depressive symptoms characterizes dieters progressing to eating disorders. As the evidence implicating dieting in the origin of eating disorders becomes stronger so strategies for primary prevention become clearer.


Reproductive functions in eating disorders.

This article reviews current knowledge about the effects of anorexia nervosa, bulimia nervosa and partial syndromes on ovulation, menstruation, sexuality, fertility, pregnancy and fetal-infant health. Eating disorders may result in failure to ovulate, oligomenorrhea, amenorrhea, reduced sex drive, infertility, hyperemesis gravidarum, low maternal weight gain in pregnancy, small babies for gestational date, low birth weight infants, increased neonatal morbidity and problems in infant feeding. The available information suggests that clinicians should inquire about nutritional intake, a history of eating disorders and weight reducing behaviours as part of the routine assessment of patients with the disorders of reproductive function listed above. If an eating disorder is discovered before conception, the woman should be encouraged to delay pregnancy until the eating disorder is treated and effectively under control. If the woman is pregnant, early diagnosis and treatment are essential to reduce maternal and fetal complications. The infants of eating-disordered women should be carefully followed to ensure adequate nutritional intake. Problems in reproductive function related to eating disorders offer rich opportunities for multispecialty collaboration in primary and secondary prevention programmes directed toward both mother and infant.