Innervation of the vasa nervorum: changes in human diabetics. Transperineurial and epineurial vessels are innervated by plexuses of unmyelinated axons. Human sural nerve biopsies were examined ultrastructurally and immunocytochemically with an antibody which recognizes a neuronal and neuroendocrine protein, PGP 9.5, to characterize perivascular axons of these plexuses. Diabetics exhibited a greater degree of abnormal innervation of the vasa nervorum than nondiabetics with and without neuropathy. Abnormal innervation included: a reduction in the percentage of vessels exhibiting perivascular axons and a concomitant increase in the percentage of vessels having denervated Schwann cell units, particularly around vessels confined to perineurial compartments, and remaining axons in nerves from diabetics exhibited fewer varicosities. Denervated arterioles of diabetics also displayed structural changes indicating injury. The arteriolar structural defects and loss of neurogenic control of neural blood flow may lead to or aggravate endoneurial ischemia or hypoxia. The patchy, focal endoneurial fiber loss that is prominent in proximal nerves and associated with the distal myelinated fiber loss of some diabetic patients may be due in part to perivascular denervation of the vasa nervorum.


Parenting classes: focus on discipline.

Parenting classes: focus on discipline. Nurses in community settings have an opportunity to provide instruction related to health and life-style needs. An important consideration is the parental role. A particularly controversial and opinion-laden aspect of parenting is disciplining children. Discipline provides children with the security of clearly enforced rules to help them learn self-control and social standards. Parenting classes are worthwhile for people who have little formal or informal preparation. A survey of middle-class elementary school district parents' and childrens' attitudes toward discipline was conducted to develop meaningful parenting classes. Parents' feelings about being a mother or father were surprisingly negative. A parent educational program was developed to cover child growth and development and disciplinary practices. Parent evaluations led to continuation and an expansion of this program to other schools within the area.


Community health assessment tool: a patterns approach to data collection and diagnosis. Creation of an assessment tool to apply Gordon's functional patterns to the community as a client was a rewarding and stimulating project. Through use of the CHAT, students developed an appreciation of the complexity and inter-relationship of numerous aspects of the community. They completed the nursing process by developing appropriate nursing diagnoses, and planning, implementing, and evaluating a health promotion project. As the students continue to use this tool in the health promotion course, the diagnoses which they generate are being collected. From this accumulated input the plan is to compile a list of common diagnoses which are appropriate to use when the community is the client.


Health needs of a suburban community: a nursing assessment approach. Community health nursing can play an important role in conducting community needs assessments that provide critical data upon which programming, planning, and evaluation should be based. The community health services developed for any given community should be planned with the specific needs of the community residents in mind. A community needs survey is one method that should be periodically employed to ascertain the specific needs and concerns of community residents. Nursing conceptual models developed by CHNs are very appropriate to the assessment of all aspects of community life related to health and well-being. Comprehensive community needs surveys should include assessment of environmental, psychosocial, and physiological aspects of health as well as indicators of health-related behaviors in the population. The Omaha classification system adapted for this study provides a broad conceptual framework that facilitates the development of comprehensive programs of assessment. Public health services are in a state of crisis in many states. Traditional program offerings may no longer be the key to providing the types of services most needed by some communities. Analysis of data on problems related to personal and family well-being in one upper middle class suburban community indicate a need for health promotion and services focused on many of the psychosocial aspects of health. The stress experienced by younger community residents appears to be related to issues of parenting and balancing the dual roles required at work and home. Families of elders are also confronted by issues concerning the decreasing independence of these individuals and the need to find additional support services for them. Community health services must be designed that take these factors into account. Professional nurses can provide the leadership necessary to assess health needs and current public health practices in these communities and to recommend and implement programs appropriate to the needs of the present and the goals of the future.


Primary, secondary, and tertiary prevention in reducing pesticide-related illness in farmers. American farmers are a specific population with specific health concerns, and there is little in the literature that addresses nursing care of farmers. The farmer needs to be educated and assessed for the potential of poisoning injury related to pesticide exposure. Studies done by the National Cancer Institute (NCI) and others have shown a somewhat greater risk of specific cancers in farmers using pesticides. Acute exposures and chronic conditions resulting from years of exposure to pesticides are oftentimes not attributed to pesticides. By use of the nursing process, nurses can develop programs at all levels of prevention to deal with this problem. This article describes such programs, as well as providing resources useful in their development.


The clinical presentation of intracranial abscesses. A study of seventy-eight cases. From 1980 through 1991, 78 patients with brain abscess were treated at the Cukurova University School of Medicine Department of Neurosurgery by surgical excision and antimicrobial therapy. Males predominated in all age groups. Although only 17 percent had a predisposing conditions such as local sinus infection, cyanotic heart disease, the majority of the cases had some evidence of a systemic infection such as peripheral leucocytosis and elevated erythrocyte sedimentation rate. The correct diagnosis was commonly not considered despite to these clues of an infective process on admission. The operative mortality was 20% which was similar to the other series reported in the literature. However in spite of significant progress with the advent of computerized tomography, microbiology and antibiotic treatment, difficulties in early diagnosis are held to be responsible for the residual high mortality. Although the appropriate antibiotic therapy, adjuvant medical therapies to control perioperative brain swelling, and the application of reliable surgical techniques have decreased the mortality and morbidity rates, the best result can only be obtained to a wider number of patients if the physician remains alert to the possibility of an intracranial abscess.


Delayed recovery from indirect optic nerve injury. A report of two unusual cases. Two patients with indirect optic nerve injury are reported. In one, head injury was minor, while in the second, the head injury was severe. Both the patients had immediate type of optic nerve injury with complete visual loss. CT scans for the orbit and optic canal were normal. Visual evoked potentials (VEP) repeatedly performed in the first 6-8 weeks were absent in both the patients. Onset of visual recovery was very late, in first case it was noticed after 12 weeks and in the second case visual recovery started after 8 weeks. Both the patients had partial visual recovery.


Craniosynostosis: surgical treatment during the first year of life. Out of 276 children with craniosynostosis operated on in a 9 year period, 231 were operated on under 1 year of age. According to the sutures involved in the process of early fusion, two groups of infants were individuated. Patients belonging to the first group were characterized by the involvement of the sagittal suture, while infants of group II presented with a synostosis of the anterior or posterior sutural complex. Two different techniques were required for the 2 groups of subjects, the first of them being mainly based on linear craniectomies, the second requiring more complex reconstructive surgical procedures. The morbidity, mortality and recurrence rates of the series were low, demonstrating that infants can tolerate the procedure as well as older children. The advantage of the early treatment consists of a better cosmetic result with a more physiological growth of faciocranial skeleton.


Cavernous angioma of the pineal region.

Cavernous angioma of the pineal region. The pineal region is one of the most rare localizations of intracranial cavernous angiomas, with only 8 cases reported up today. The Authors report a case of cavernous angioma of such localization and review the pertinent literature. Magnetic resonance allows the correct diagnosis of cavernous malformations on the basis of their typical aspect, even in the absence of histological verification. We suggest that this imaging technique will allow to identify more frequently pineal cavernomas preoperatively, thus avoiding useless irradiation.


Solid supratentorial haemangioblastoma. Case report. A rare case of solid supratentorial haemangioblastoma presenting in a 67-year-old female with psyco-motory lowering, dysphasia and mild haemiparesis is reported and the pertinent literature is reviewed. The distinction between angioblastic meningioma and haemangioblastoma with the non specific radiological findings of this supratentorial uncommon tumour in are also debated.


Pseudotumor cerebri. Lumboperitoneal shunt in long lasting cases. The Authors report three cases of pseudotumor cerebri with noteworthy visual defect. Lumboperitoneal shunt enables good recovery where there was no atrophy of the optic nerve and demonstrated its usefulness also in serious situations.


Diastasis of the maxillary bone: an unusual complication of transsphenoidal surgery. Diastasis of the intermaxillary suture is an unusual complication of the transsphenoidal approach to the sella turcica. Over the 1977-1989 twelve-year-period, 192 procedures were performed at our Center. This complication occurred only once, in a senile patient with marked osteoporosis. It did not alter the course of the operation, nor did it create additional problems during the postoperative period.


Associated cervical schwannoma and dorsal meningioma. Case report and review of the literature. The association between spinal meningiomas and neurinomas without clinical signs of neurofibromatosis is very rare with only four cases reported in literature. A case of 70-year-old woman with a history of progressive paraparesis is presented. A cervico-dorsal magnetic resonance with contrast showed two tumors with different enhancement. The patient had examination negative for neurofibromatosis. At histological examination cervical schwannoma and a dorsal meningioma were found. The Authors debate the rarity of this association, the possible pathogenesis and the MR findings.


An overview of continuous infusion chemotherapy. Chemotherapy administered by continuous infusion has been shown to be more effective and less toxic than bolus therapy in many instances. Because of advances in infusion-pump and access-device technology, most patients receive their chemotherapy as outpatients. Careful patient selection and comprehensive patient teaching are essential to ensure the success of continuous infusion chemotherapy delivery.


Metastasis of breast carcinoma to intracranial meningioma. Case report and review of the literature. A case of metastasizing breast carcinoma to an intracranial meningioma is presented. The pathogenesis and principles of diagnosis of this rare occurrence are discussed in light of the data reported from the literature.


High-dose ifosfamide and mesna therapy in the outpatient setting. Ifosfamide and mesna as a chemotherapeutic and protective combination has increased oncologists' choice of agents in the treatment of various forms of cancer today. Additional responsibility is placed on both patient and caregiver when high doses of these drugs are administered in an outpatient setting. Of utmost importance is the education of the patient and the caregiver in their immediate responsibilities, as well as required procedures after the course of the drug has been completed. In this article, areas of concern to the patient and caregiver are described in detail. Initial therapy and any subsequent side effects are managed on an outpatient basis except in rare circumstances.


The impact of a nutritional support team on the cost and management of multilumen central venous catheters. Total parenteral nutrition (TPN) is most commonly delivered into a large vein through a central venous catheter (CVC). Because complications associated with CVCs may be life threatening or costly to the patient and the medical facility, proper care and maintenance of a CVC is essential. A 12-month retrospective study was conducted by a nutritional support team to evaluate cost effectiveness of CVC care in patients receiving TPN. Certain factors, such as catheter type and location, duration of usage, number of catheters, physician who placed the catheter, and complications were recorded for each patient receiving TPN. All CVCs used for TPN were maintained by a member of the nutritional support team. A total of 434 CVCs were placed in 277 patients who required TPN (average, 1.6 catheters/patient; range, 1-10 catheters/patient). Specific catheter-related data, and occurrences of complications were recorded on a flow sheet designed specifically for patients requiring TPN. Major complications (those which potentially increased mortality and morbidity) and minor complications (those that did not prolong hospitalization) were distinguished and the average cost of these complications was determined based on actual patient charges. Major complications occurred in 5% of the catheters placed, including: pneumothorax, thoracic duct fluid leak, artery laceration, malposition, failed attempts, and catheter-related sepsis. Catheter-related sepsis occurred in only 0.5% of patients, compared with a reported incidence of 5%, and cost an average $20,200. Thus, complications of CVC may be reduced when maintenance is provided by a skilled clinician or specific team, decreasing the cost, as well as improving the quality of care.


Current perspectives on intravenous administration of digoxin. Cardiac glycosides were used as early as the first century A.D. The most commonly prescribed compound of this family is digoxin, because of its relatively short half-life. Intravenous digoxin has high utility 1) for instances in which digitalization must be rapidly accomplished; 2) when oral digitalization is not feasible; and/or 3) as augmentation therapy to other medication protocols. Myocardial uptake of I.V. digoxin is rapid and extensive; yet, serum half-life is approximately 34 hours, the same as in oral administration. Intravenous digoxin can be administered in divided doses every 4 to 8 hours, the 24-hour dose not to exceed 1.0 mg for a 155-pound, or 70.0-kg patient. Awareness of risk factors along with state-of-the-art technology can improve ongoing monitoring of the patient receiving I.V. digoxin.


Intramedullary cervical cavernoma. Case report. A rare case of intramedullary cervical cavernoma with complete neuroradiological examination is described. The Authors debate about clinical course, radiological examination and surgical indications.


Improved outcome for post-thoracotomy patients using intermittent bupivacaine with epinephrine by the CADD-Plus Ambulatory Infusion Pump. Comfort in the post-thoracotomy patient is frequently a major care issue. It is particularly relevant for nurses practicing in smaller institutions where physician staff are not "in house" and easily accessible. A retrospective chart audit was used to compare pain therapy in two groups of patients undergoing thoracic surgery. Group 1 patients received traditional pain control therapy primarily by the intravenous route. Group 2 patients received intercostal bupivacaine with epinephrine via the CADD-Plus Ambulatory Infusion Pump Model 5400 (Pharmacia Deltec, Inc., St. Paul, Minn). Narcotic and analgesic medication requirements, length of stay, patient perception of comfort, and nursing interventions for pain management were evaluated. The use of the CADD-Plus infusion pump was found to have a positive outcome on the recovery of post-thoracotomy patients in this institution. They had a decreased length of stay, a decreased perceived level of pain, and used less nursing time for pain control than patients treated with more traditional methods of pain control.


Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. The monoclonal antibody Ki-67 reacts with a human nuclear cell proliferation-associated antigen that is expressed in all active parts of the cell cycle. Recently we have raised monoclonal antibodies, MIB 1-3, against recombinant parts of the Ki-67 antigen. These antibodies are true Ki-67 equivalents, as demonstrated by immunostaining of fresh specimens, biochemistry, and molecular biological techniques. Formalin-fixed, paraffin-embedded sections routinely processed for immunohistochemistry failed to stain for Ki-67 and MIB 2. Antibodies MIB 1 and MIB 3 labelled mitotic figures, while non-mitotic proliferating cells were negative under these conditions. However, when dewaxed microwave oven-processed paraffin sections of formalin-fixed tissues were used, MIB 1 and MIB 3 gave strong nuclear staining of those cells presumed to proliferate under a variety of normal and neoplastic conditions. Moreover, routine decalcification or depigmentation techniques did not alter the immunoreactivity of MIB 1 and MIB 3 with microwave-processed paraffin sections. This method is highly reproducible, easy to perform at low cost, and no additional technical skill is needed because after microwave treatment just routine immunohistochemical methods are used. Since we have successfully applied this new method to sections obtained from paraffin blocks stored for a long time (in one case more than 60 years), the assessment of cell kinetics through the detection of Ki-67 antigen is now possible on archival material collected in histopathology departments all over the world.


Immunoreactivity for p53 protein in malignant mesothelioma and non-neoplastic mesothelium. The presence of p53 protein in non-neoplastic pleural mesothelium (40 cases) and in human malignant mesothelioma (36 cases) was assessed immunohistochemically using the antibodies DO7, CM-1, and PAb240. In a quarter of the malignant mesotheliomas, there was nuclear immunoreactivity for p53 protein with both the DO7 and CM-1 antibodies. There were no statistically significant differences between the various mesothelioma subtypes (P > 0.05). No immunoreactivity was found with the PAb240 antibody, suggesting absence of mutant-type p53 protein. Nonneoplastic mesothelium was not immunoreactive with any of the antibodies. We conclude that there is immunoreactivity for p53 protein in some mesotheliomas. p53 protein immunoreactivity could be used to discriminate between neoplastic and reactive mesothelium.


p53 immunostaining in the distinction between benign and malignant mesothelial proliferations using formalin-fixed paraffin sections. The distinction between reactive mesothelium and mesothelioma in pleural biopsy specimens is notoriously difficult, and conventional immunohistochemical markers have provided no relief. The object of this study was to examine the frequency of immunohistochemically detectable p53 overexpression in routinely processed, paraffin-embedded tissue from pleural mesotheliomas and from pleura showing reactive mesothelial hyperplasia, using a polyclonal antibody to formalin-resistant p53 epitopes, and to consider the diagnostic utility of this antibody in the distinction between mesothelioma and reactive mesothelium in pleural biopsy specimens. Immunostaining was enhanced by pepsin predigestion prior to the application of the primary antibody. Positivity occurred in 10/16 epithelial mesotheliomas, 9/19 biphasic mesotheliomas, 2/12 sarcomatous mesotheliomas but in none of 20 reactive pleura. Immunostaining was particularly intense in some of the biopsy specimens, which may be due to the rapidity with which these small pieces of tissue were fixed. In conclusion, this study suggests that p53 immunostaining can help to distinguish epithelial or biphasic mesothelioma from reactive mesothelial hyperplasia in formalin-fixed, paraffin-embedded pleural biopsy specimens.


Characterization of the smooth muscle cell infiltrate and associated connective matrix of lymphangiomyomatosis. Immunohistochemical and ultrastructural study of two cases. Lymphangiomyomatosis (LAM) consists of smooth muscle (SM) cell proliferation of unknown origin involving the lymph nodes and the lung interstitium. From morphological studies showing both SM differentiation of the proliferating cells and lymphatic hyperplasia, hypotheses were suggested concerning the origin of the proliferation. Two cases of LAM were investigated by electron microscopy and immunohistochemistry; tissues were obtained by lymph node and open lung biopsies. Cytoplasmic and matrix protein markers were used in order to clarify the pattern of differentiation of the proliferating cells and to characterize their connective tissue environment. The proliferating cells present ultrastructural characteristics of SM cells; they contain vimentin, desmin, and alpha-SM actin and are devoid of Factor VIII, favouring a parieto-arterial origin. The connective tissue matrix inside the infiltrate is composed of interstitial collagens and basement membrane components. At the late stage of the disease, remodelling of the interstitial matrix accompanies the infiltrate and remains perilesional.


Dominantly inherited tubular aggregate myopathy. We report an unusual familial myopathy characterized morphologically by the presence of large tubular aggregates in all fibre types. Two patients, a father and daughter, presented with slowly progressive proximal weakness, limitation of eye movement, and Achilles tendon contractures. Serum creatine kinase was 5-10 times normal. Light microscopy revealed type I fibre predominance. Basophilic accumulations, which stained intensely with the NADH-TR reaction, were present in both fibre types. Electron microscopy revealed that these consisted of tightly packed parallel tubular arrays. These varied somewhat in their ultrastructural appearance and were classified accordingly as type I, II, and III tubular structures. The tubular aggregates appear to be derived from the sarcoplasmic reticulum. This report further supports the evidence of a distinct clinico-pathological entity of genetic origin.


Localization of CEA messenger RNA by in situ hybridization in normal colonic mucosa and colorectal adenocarcinomas. Carcinoembryonic antigen (CEA) mRNA expression was studied in 14 cases of normal colorectal mucosa and colonic adenocarcinomas using in situ hybridization with a 32P-labelled cDNA probe to the unique 3'-untranslated region of CEA. This approach has the advantage that the target mRNA remains in the cell of origin, whereas there is considerable ambiguity in immunocytochemistry data for CEA because the protein is secreted. Furthermore, the specific cDNA probe overcomes potential problems of immunological cross-reactivity with other members of the CEA family. The results demonstrated that abundant, heterogeneously distributed CEA mRNA was present in colorectal adenocarcinomas, with the highest levels in cells lining glandular structures. Parallel immunohistochemistry with anti-CEA monoclonal antibody A5B7 showed that the regions of tumours with the highest levels of CEA mRNA also had the highest CEA protein levels, suggesting that the heterogeneous distribution reflects CEA expression rather than differential secretion of the protein. In the normal colonic mucosa, CEA mRNA expression was observed in surface epithelial cells and goblet cells of the upper crypts, with very low hybridization in the mid crypt and at the base. This crypt-surface distribution was identical to that observed for CEA protein. In situ hybridization therefore confirms that high levels of CEA mRNA are expressed in differentiated surface epithelial cells of the normal colon.


Policy options: early intervention services for substance-exposed infants. Substance-exposed infants, or babies that have been victims of their mothers' drug use during pregnancy, have reached substantial proportions. Currently, no comprehensive public policy exists to deal with these infants as they enter a society unprepared to respond to an issue increasingly fraught with substantial adverse economic, social, and political ramifications. In order to address the needs of this emerging sub-population, California's governor and state legislature must develop and adopt a concerted interagency policy which outlines: a) uniform criteria for local health care workers, social service agencies, and educators; b) consistent guidelines governing the exchange of information among a range of agencies, including hospitals, schools, and other public and private agencies; and c) increased prevention and early intervention services for these babies and their families. Addressing the needs of these infants requires a bold, comprehensive, interdisciplinary approach from the creators of public policy.


Impact evaluation of Drug Abuse Resistance Education (DARE). The purpose of this study was to assess the impact of Drug Abuse Resistance Education (DARE) on fifth-grade students in the Long Beach Unified School District in Long Beach, California. The research suggests that DARE does not significantly change the amount of drug use, which is minimal at the fifth grade level. In general, children receiving DARE during the study period maintained existing levels of drug abuse. Approximately 3,000 students participated in the study. A pretest and posttest self-report survey was utilized during the Fall 1989 semester for experimental and control groups. As DARE programs gain popularity in other school districts, school administrators need more information on the program to decide if DARE should be presented in their schools. Administrative decision-making must consider program effectiveness and curriculum time constraints.


Youth's recreation and drug sensations: is there a relationship? Adolescents' social behaviors remain a mystery to parks and recreation providers. Adolescence is a "high-risk" time for all youth in terms of experimenting with potentially health-compromising behavior, whether alcohol, drugs, or sex. Most of these antisocial behaviors occur during adolescents' leisure time. These inferences gave impetus to this research effort. The study was designed to ascertain information on adolescents' preferences for pleasure: drugs or recreation. Data were collected from a sample of 100 high school students from a medium-sized college town, and 100 students from a rural town in Florida. Findings revealed four statistically significant associations in the motives or pleasures sought in recreation and in drug behaviors: "enhancement of popularity," "provision of a means for self-discovery," "achievement of personal goal," and means to rebel against parents. In reference to the latter motive, findings revealed that neither drugs nor recreation were used to rebel against parents. Findings also provide documentation of the value of recreation in insulating adolescents against many of the stressors of contemporary life.


Women as home caregivers: gender portrayal in OTC drug commercials. Concern has long been expressed over possible adverse effects of television advertising of over-the-counter (OTC) medicines. This study investigated a sample of prime time network television ads to determine how gender portrayals differed in drug and non-drug commercials. Findings indicated that women were significantly more likely than men to appear as characters in drug ads than in ads for other products, and that they are frequently portrayed in these commercials as experts on home medical care, often as mothers caring for ill children. This supports the hypothesis that drug advertisers take advantage of stereotypical images of women as home medical caregivers. It also raises the question of whether female consumers are being encouraged by these ads to overuse OTC medications as a way of gaining the family's love and respect.


Risk factors for drug use in rural adolescents. This study tested the relevance of a risk factor model for predicting drug use among rural adolescents. A questionnaire battery assessing drug use and the presence/absence of twenty risk factors derived from a previous study of urban adolescents was administered to a sample of seventh graders (N = 235) in the public school system of a rural community. All but one of these risk factors were found to be significantly related to at least one category of drug use. In addition, a risk factor index based on a subset of ten risk factors was significantly associated with the prevalence and frequency of use for cigarettes, beer and wine, hard liquor, marijuana, and other drugs. These findings support the generalizability of a risk factor approach to predicting drug use, and underscore the need for increased prevention and research efforts directed at rural adolescents.


"The responsibility to inform, the power to act": a conference for New England college newspaper editors on the role of the campus press in addressing substance use issues. College newspapers are a powerful but underutilized medium for educating students on health issues, including those related to drug and alcohol use on campus. Editors of these publications are in a position to wield significant influence among their readers. In addition to communicating factual information about the prevalence and impact of substance use among college students, editors can use the press to advocate changes in students' attitudes and behaviors and in college or community policies that affect substance use. A pilot conference was held to help New England college newspaper editors perceive the importance of their role in educating their peers about substance use and other health-related issues, and to offer concrete suggestions as to how they can incorporate these topics into an "activist" campus press.


Screening for patients with alcohol problems: severity of patients identified by the CAGE. Primary care physicians are well situated to identify patients with substance abuse problems and motivate them to seek appropriate assistance, but active programs are the exception. A study in a community setting was undertaken to assess the CAGE (the first letters of key words in a series of four questions about drinking: cut down; annoyed; guilty; and eye-opener), instrument in the routine screening for alcohol problems in both new and established patients. The screening process identified subjects for a pilot evaluation of a motivational interview designed to encourage problem-solving behavior. This article focuses on the screening results and the use of the CAGE instrument. During June and July of 1990, 687 patients of two primary care physicians belonging to a large group practice were asked to complete a health questionnaire that included the CAGE. Those who responded affirmatively to at least two of the four CAGE questions were requested to participate in follow-up assessment of problems associated with alcohol and health. The type and severity of alcohol problems experienced by patients who scored positive on the CAGE are described. Prevalence of a positive score on the CAGE was 8.6 percent with males, smokers, and blue collar and unemployed persons being more likely to score positive. The positive predictive value was .68. Primarily, persons with moderate alcohol problems were identified. Results show that the CAGE instrument is a useful screening device for identifying those with mild to moderate substance abuse problems, increasing the opportunity for intervention prior to serious medical complications. The instrument is easily administered, and has demonstrated relatively high levels of sensitivity and specificity. When combined with assessment and motivational interviews, the CAGE shows promise in the secondary prevention of substance abuse and related health problems.


Academically successful drug users: an oxymoron? The present study examines substance use among academically successful students. The data were collected in two discrete anonymous surveys of 2,288 ninth-grade and 2,653 eleventh-grade California students, and 1,043 ninth-grade and 862 eleventh-grade students from a large suburban county. Over 70 percent of the academically successful students from both samples reported some type of drug use. These successful students were divided for comparison into three groups according to their involvement with drugs: abstainers, conventional users, and high-risk users. The analyses indicated that the negative association between drug use and academic achievement may be counter-balanced by mediating factors identified in the study. These factors included high "educational aspiration," "parent educational level," and "emotional stability."


Parental response to cystic fibrosis: a contextual analysis of the diagnosis phase. A contextual framework guided the measurement of specific stressors encountered by parents of children recently diagnosed with cystic fibrosis (CF). Three variables were assessed within the context of the parenting role: illness-specific tasks, normal parenting tasks, and strains in family roles. These situation-specific stressors were contrasted with global measures of parenting stress in their ability to predict depression. Sixty-four parents (36 mothers, 28 fathers) of infants and toddlers recently diagnosed with CF completed a structured interview and standardized measures in the home. Parents reported elevations in both situation-specific and global parenting stress, and a greater number of depressive symptoms than a norm group. Mothers reported significantly greater strain in managing their caregiving role and higher levels of depression than fathers. Controlling for situation-specific parenting stress and marital satisfaction, regression analyses indicated that role strain related to CF was associated with greater depression in mothers, but not fathers. Furthermore, stressors measured contextually rather than globally accounted for substantially greater proportions of the variance in depression. The findings highlight the need to measure ongoing strains specific to the medical condition, and to assess role-related changes.


Functioning among mothers and fathers of children with juvenile rheumatic disease: a longitudinal study. Examined the adaptation of mothers and fathers of children with juvenile rheumatic disease on two occasions, 1 year apart, using 159 married couples at Time 1, and 111 of these couples at Time 2. A stress and coping model was tested in which parental functioning is determined by ongoing life stressors (patient and spouse dysfunction), family resources, and parents' illness-related coping. Mothers reported more depression than fathers did. However, poorer concurrent functioning among both mothers and fathers was explained partly by patients having more functional disability, pain, and psychosocial problems. In addition, spouse's dysfunction and the parent's use of avoidance coping were related to poorer parental adaptation, both concurrently and 1 year later. The implications of the findings for developing stress and coping models of parental adaptation to having a chronically ill child, and for intervention strategies with parents, patients, and families, are discussed.


Children with physical handicaps and their mothers: the interrelation of social support, maternal adjustment, and child adjustment. Examined the interrelation of maternal adjustment, mother-child interaction, and child adjustment in 29 families of children with spina bifida and without mental retardation and in 28 families of children without handicaps. A multivariate, ecological model proposed that adjustment of mother and child depends on the adaptiveness of maternal response to the stress of the physical handicap and on the ability of mothers to create an optimal caregiving environment through mother-child interaction. Analyses examining the relationships among maternal social support, maternal psychological adjustment, and child adjustment are reported. Social support was found to be related to higher maternal psychological adjustment and to higher child adjustment, and maternal psychological adjustment was related positively to child adjustment in both groups. No significant differences were found between groups in the examined relationships or in the levels of resources and adjustment. Results underscore strengths of families of children with spina bifida in their adaptation to the stress of the handicap.


Psychological adjustment of children with cystic fibrosis: the role of child cognitive processes and maternal adjustment. Found 60% of children 7-12 years old with cystic fibrosis to have a parent-reported behavior problem and 62% met the criteria for a DSM-III diagnosis based on a structured clinical interview with the child. Mixed internal and external behavior problem patterns and diagnoses of anxiety and oppositional disorder were most frequent. Support was provided for the hypothesized psycho-social/mediational roles of child perception of self-worth and maternal anxiety in child adjustment. Together, the variables of the transactional stress and coping model accounted for 39 and 43% of the variance in mother-reported internalizing and externalizing behavior problems and for 68% of the variance in child-reported problems.


Perceived control as a predictor of distress in children undergoing invasive medical procedures. Children's anticipatory attributional assessment of the source(s) of perceived control is hypothesized to play an important role in the etiology of distress in children undergoing invasive medical procedures. Four perceived control types, based on learned helplessness theory, are specified by a conceptual model that guides this research: Mutual, Powerful Other, Personal, and Unknown. Among 73 children between the ages of 4 and 18 having their blood drawn, it was predicted that children with an attributional analysis of unknown perceived source of control prior to the impending medical procedures would experience a heightened level of anxiety (procedure-related distress). As predicted, children with an anticipatory attributional assessment of unknown perceived control interfered with or extended the medical procedure significantly more (41%) than children who could attribute some perceived source of control (13%). They were also rated by themselves, the parents, and a trained clinical observer as manifesting significantly greater (p < .05) anticipatory procedural distress using both cognitive (subjective) and behavioral (objective) assessment perspectives. These findings were independent of children's age. This paper supports the need for additional theory-driven research and the importance of investigating the role of attributional variables in the etiology of procedure-related distress in children.


Peer influences in pediatric chronic illness: an update. Examined research on peer relations of children with chronic illness. In general, scant attention has been devoted to this topic. A recent review (La Greca, 1990) highlighted this oversight and suggested several avenues for further research and clinical endeavors. This paper updates the earlier review, and provides examples from current literature regarding the role of peer relations in adjustment to chronic disease. Data are presented from an ongoing investigation of the ways in which friends and family members provide support for adolescents with diabetes. Adolescents' friends were more oriented toward companionship support than were family members; both family and friends were reported to provide emotional support for diabetes care, although the types of emotional support varied. Findings are discussed in the context of the important and varied role that peers play in youngsters' disease adaptation.


Vale dictum: an editor's view of the field of pediatric psychology and its journal. Examines activities of Editor of the Journal of Pediatric Psychology for issues published 1988-1992. Articles published during term are analyzed in terms of senior author gender, affiliation, academic rank, grant support, theoretical orientation, population type, population age, article type, and research purpose. Comparisons are made to earlier analysis of article trends in Journal by Elkins and Roberts (1988). A summary is provided of what the Journal reflects about pediatric psychology in terms of clinical practice, scientific research, and professional issues.


Influence of melatonin on the proliferation of hepatoma cells in the Syrian hamster: in vivo and in vitro study. A study was carried out to determine the possible influence of melatonin on the proliferation of Kirkman-Robbins hepatoma cells in Syrian hamsters, both in vivo and in vitro. A highly significant inhibition of the proliferation of transplanted hepatoma cells was observed in vivo following melatonin administration (proliferation index 10.3 +/- 1.5; mean +/- SD) in comparison with controls (proliferation index 23.3 +/- 2.2), whereas in vitro melatonin (at concentrations of 10(-5)-10(-11) M) was ineffective. These results indicate that inhibitory effect of melatonin on transplantable hepatoma cells in vivo may be indirect.


Diurnal variations of urinary 6-sulphatoxymelatonin in male intact or ganglionectomized mink. The existence of the major urinary metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s), was validated for mink and the 24 hr urinary excretion pattern was determined in intact and superior cervical ganglionectomized animals under different photoperiodic conditions. Within- and between-assay variations, parallelism between serially mid-night pooled urine dilutions and standard curves in aMT6s free urine of mink at 1:125 dilution and recovery of aMT6s in mid-day pooled urine at 1:125 dilution provided a good validation for the mink urinary a MT6s assay. In natural photoperiods (January, LD 9:15; April, LD 13:11) the diurnal rhythm was characterized by low aMT6s values during the day and high values at night. There were no differences in the nocturnal values measured under long- (April, 4.11 +/- 0.40 ng/hr) or short-day (January, 4.74 +/- 0.36 ng/hr) conditions. In an experimental long photoperiod (LD 15:9), the same result was obtained on the 24 hr rhythm in intact animals, but in ganglionectomized mink the nocturnal rise in aMT6s was abolished and the nocturnal values were always low (0.88 +/- 0.09 ng/hr). Our results agree with those obtained in other species concerning plasma melatonin rhythm and urinary aMT6s excretion; we thus conclude that this is an effective assay for measuring pineal activity in mink.


A phase-dependent delay of the chick pineal rhythm in rate of thymidine incorporation by brief exposure to aphidicolin. Cultured chick pineal glands show a persistent rhythm in the rate of cumulative incorporation of thymidine into DNA. In this study we have examined the effects of pulse-exposure to aphidicolin in the dark on the first day of culture on thymidine incorporation during the second and third days of culture in the dark with aphidicolin-free medium. The phase of the rhythm in the rate of thymidine incorporation was delayed in a concentration-dependent manner by a 4-hr exposure to aphidicolin, commencing in the final hour of the photoperiod. This effect was phase-dependent and not seen when exposure to aphidicolin began earlier in the photoperiod.


Effects of pinealectomy on wool growth and wool follicle density in merino sheep. There is evidence to indicate that pinealectomy may enhance wool growth in the sheep. The aim of this study was to determine the effect of pinealectomy on wool growth and wool follicle density in Merino sheep. Castrated Merino rams (4 months old) were either pinealectomized (P), sham-pinealectomized (S) or not treated (C). Wool growth on mid-side patches was measured every 4 weeks and follicle density was monitored in skin biopsies collected before treatment and at regular intervals for 60 weeks. Venous blood samples were taken on each of these occasions for prolactin analysis. Melatonin concentrations were determined in venous blood collected pre- and posttreatment from samples taken over a 24-hr period during the winter solstice. Pre- and posttreatment plasma melatonin levels (mean +/- SEM) 65 +/- 17 and < 13 pg/ml for P, 86 +/- 21 and 69 +/- 20 pg/ml for S, and 94 +/- 41 and 122 +/- 37 pg/ml for C, respectively, indicated that the pineal glands had been successfully removed. Wool growth, total follicle density and liveweight (mean +/- SEM) did not differ between treatment groups. Measurements at week 60 were 3.9 +/- 0.3, 4.1 +/- 0.2, and 3.8 +/- 0.3 gm clean wool/100 cm2; 66 +/- 6, 69 +/- 7, and 64 +/- 3 follicles/mm2; and 50.4 +/- 1.3, 50.8 +/- 1.4, and 52.6 +/- 1.1 kg liveweight for groups P, S, and C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Participation of the pineal gland in sexual maturation of female rainbow trout (Oncorhynchus mykiss Walbaum). In the study rainbow trout, pinealectomized at two different periods of their sexual cycle, i.e., at either 1 or 5 months before spawning, were studied. It was found that the lack of the pineal gland in the period directly preceding the spawning had no statistical effect on either spawning or the number of females that produced eggs. Pinealectomy performed during vitellogenesis delayed spawning by about 2 weeks and resulted in the absence of ovulation in 20% of the females. The results suggest that the pineal gland may influence the hypothalamo-pituitary-gonadal axis by altering the maturation period and controlling spawning in the rainbow trout.


[New hypotheses for the mechanisms of streptozotocin and alloxan inducing diabetes mellitus]. We propose new hypotheses for the mechanisms of streptozotocin (STZ) and alloxan inducing experimental diabetes in animals. STZ is transported into pancreatic beta cells through glucose transporter in the cell membranes and attacks mitochondria. Mitochondrial ATP generation is inhibited and the resulting high concentration of intracellular ADP causes its degradation providing hypoxanthine, a substrate of xanthine oxidase (XOD) whose activity is intrinsically very high in beta cells. Then, XOD-catalyzing reaction is proceeded as proved by increased formation of uric acid and O2- radicals are produced, but beta cells are inefficient to scavenge these radicals because of their extremely low activity of superoxide dismutase. On the other hand, STZ directly activates XOD and enhances O2- generation. Consequently, pancreatic beta cells are dually suffered from O2- radicals or probably hydroxyl radicals derived from the former when exposed to STZ. Allopurinol, an inhibitor of XOD, can protect animals from the diabetogenic effect of STZ. In pancreatic beta cells, alloxan anion radicals are generated from alloxan probably mediated by the action of microsomal cytochrome P-450 system. These radicals have long half-life and directly damage DNA in vitro. The widely accepted hypothesis that the cause of alloxan-induced diabetes is attributable to O2- radicals formed from alloxan is excluded, because alloxan itself shows a very potent scavenging effect to O2- radicals. Therefore alloxan anion radicals seem to be directly related to the incidence of diabetes by alloxan.


[Terpenoids and curcuminoids of the rhizoma of Curcuma xanthorrhiza Roxb]. The fresh rhizomes of Curcuma xanthorrhiza Roxb. were investigated for terpenoids and curcuminoids. Nine sesquiterpenoids, alpha-curcumene (1), arturmerone (2), xanthorrhizol (3), germacrone (4), beta-curcumene (6), beta-sesquiphellandrene (9), curzerenone (10), alpha-turmerone (11) and beta-turmerone (12), and three curcuminoids, curcumin (7), mono-demethoxycurcumin (8) and bis-demethoxycurcumin (13), were isolated and one monoterpenoid, camphor (5), was identified by capillary GC-MS. Four species of C. xanthorrhiza could be classified into two chemotypes by their bisabolane-type sesquiterpenoid compositions. The first type contained large amounts of 2, 11 and 12 (CX I type). The second type contained large amounts of 1, 3 and 6, and none of 2, 9, 11 and 12 (CX II type). These two chemotypes, CX I type and CX II type, were compared with the two chemotypes of C. longa L., CL I type and CL II type, on their contents by capillary GC and HPLC analysis. It was found that all of them contained curcuminoids, 7, 8 and 13 and large amounts of various bisabolane-type sesquiterpenoids.


[Strain differences of mice in learning of swimming behavior and effect of hemicholinium and vasopressin. Observation by a simple water maze apparatus]. In order to determine the strain differences in learning of swimming behavior and to study the influence of vasopressin or its derivatives on hemicholinium-3-induced impairment of water maze learning in mice, we designed a new apparatus using water maze which has three panels in small fish breeding water bath (L60 x W30 x H36 cm). In the first swimming, six strains of adult male mice, ICR, ddY, ddN, C3H/He, BALB/C and C57BL were subjected to learn swimming behavior twice a day for 6 d in a straight course. Only ICR, ddN, C57BL and BALB/C strain mice were chosen for the next experiment. In the second swimming, mice (ICR, ddN, C57BL, BALB/C) were swum in the water maze apparatus. Scopolamine-induced impairment of water maze learning was produced only in ICR, BALB/C mice, but not in C57BL and ddN strain, which was recovered by physostigmine. Amnesia was not obtained by intracerebroventricular injection (i.c.v.) of cycloheximide and AlCl3 in mice (ICR). Hemicholinium-induced amnesia was improved by vasopressin and desmopressin. Lysine-vasopressin and oxytocin were without affecting hemicholinium-induced amnesia. Pretreatment with a vasopressin antagonist, ([1-(beta-mercapto-beta,beta-cyclopenta-methylene propionic acid), 2-(o-methyl)tyrosine arginine]-vasopressin) resulted in a reversible effect on the improvement of hemicholinium-induced amnesia by vasopressin. Of four different strain mice, ICR mice were the most preferable to the presently used test. They were also more responsive to hemicholinium and vasopressin than the other strains. These results suggest that the simple water maze apparatus may be useful for a pre-examination of nootropics or a study of learning of swimming behavior in mice.


[The effect of etoposide on influx and efflux of cytosine arabinoside in P388 murine leukemic cells]. We studied the effects of etoposide on the influx, intracellular accumulation and efflux of ara-C in P388 leukemic cells. Etoposide inhibited the active influx of ara-C in a dose dependent manner, and the inhibition was reversible. Etoposide also affected the intracellular accumulation of ara-C, though its inhibitory effect for the intracellular accumulation was weaker than that for the influx of ara-C. It was also shown that etoposide inhibited the active efflux of ara-C. Furthermore, etoposide inhibited the active transport of ara-C bidirectionally but the insensitive route of etoposide existed especially at high concentration of ara-C. The effect of inhibition of the transport of ara-C on the accumulation of ara-C was more significant at lower concentration of ara-C. Judging from the drug concentrations used in this study, an interaction between etoposide and ara-C could occur in the clinical treatment.


[Assay of flow cytometry for the effect of cepharanthine on resistance to doxorubicin]. The biochemical activity of cepharanthine and the possible mechanism by which it reverses the resistance to doxorubicin in P388 leukemia cells were examined in vitro. The microfluorometric analysis of the cellular level of doxorubicin in drug-resistant cells showed that cepharanthine markedly enhanced the sensitivity of doxorubicin against resistant cells in the cellular level. Cepharanthine also enhanced the inhibitory effect of doxorubicin on the incorporation of thymidine into DNA in resistant cells. The analysis of DNA histogram obtained by flow cytometry showed that doxorubicin exerted its growth-inhibitory effect by blocking the cell cycle at the G2 phase in P388 cells. At higher concentrations, doxorubicin prolonged the S phase and inhibited cell cycle progression to the G2/M phase in cells. The treatment with cepharanthine potentiated these blocking effects induced by doxorubicin in cells. It seems that the modifications of the biological effect of doxorubicin by cepharanthine are due to the change of their ability to induce DNA damage in cells.


[Pharmacological study on Panax ginseng C. A. Meyer. XIV. Effect of 70% methanolic extract from red ginseng on the cytocidal effect of mitomycin c against rat ascites hepatoma AH 130]. The influence of the 70% methanolic extract (RMe) from Red Ginseng (a steamed and dried root of Panax ginseng C. A. Meyer) on the antitumor activity of mitomycin C (MMC) against rat ascites hepatoma AH 130 was investigated. In the case of a solid tumor, RMe at oral doses of 200, 500 mg/kg showed an inhibitory effect, but RMe was ineffective in the case of an ascites tumor. MMC combined with RMe showed a stronger antitumor effect than MMC alone. Moreover, RMe inhibited the pulmonary metastases of the tumor cells, as well as the decrease of blood platelet counts and of the fibrinogen level induced by the infusion of the tumor cells in rats. Furthermore, RMe promoted the uptake of MMC into the tumor cells and enhanced in vitro the cytotoxicity of MMC against the cultured tumor cells.


[Pharmacological study on Panax ginseng C. A. Meyer. XV. Effects of 70% methanolic extract from red and white ginseng on the antitumor activity of mitomycin C]. The influence of various fractions and ginsenosides from the 70% methanolic extract (RMe) of Red Ginseng (a steamed and dried root of Panax ginseng C. A. Meyer) on the cytocidal effect of mitomycin C (MMC) against Ehrlich ascites carcinoma was investigated in vitro. The AcOEt soluble portion (RMe-I) showed an increasing effect on the activities of lysosomal enzymes in the cultured tumor cells. RMe-I promoted the uptake of MMC into the tumor cells and enhanced the cytotoxicity of MMC against the cultured tumor cells. 20(S)-, 20(R)-ginsenoside Rg3 and ginsenoside Rh2 isolated from RMe-I promoted the uptake of MMC into the tumor cells but ginsenosides from the n-BuOH soluble portion (RME-II) had no effect. Furthermore, the influence of RMe and the 70% methanolic extract (WMe) from White Ginseng (a dried root of Panax ginseng C. A. Meyer) on the cytocidal effect of MMC was investigated in vivo. MMC combined with RMe showed stronger antitumor effects against the ascites form of mouse Ehrlich ascites carcinoma and rat ascites hepatoma AH 130 than MMC combined with WMe. The activities of lysosomal enzymes in tumor cells were also more increased in comparison with that combined MMC and WMe.


The effect of inspiratory muscle fatigue on breathing pattern and ventilatory response to CO2. 1. The effects of inducing inspiratory muscle fatigue on the subsequent breathing pattern were examined during resting unstimulated breathing and during CO2 rebreathing. In addition, we examined whether induction of inspiratory muscle fatigue alters CO2 responsiveness. 2. Global inspiratory muscle fatigue and diaphragmatic fatigue were achieved by having subjects breathe against an inspiratory resistive load while generating a predetermined fraction of either their maximal mouth pressure or maximal transdiaphragmatic pressure until they were unable to generate the target pressure. 3. Induction of inspiratory muscle fatigue had no effect on the subsequent breathing pattern during either unstimulated breathing or during CO2 rebreathing. 4. Following induction of inspiratory muscle fatigue, the slope of the ventilatory response to CO2 was significantly decreased from 18.8 +/- 3.3 during control to 13.8 +/- 2.1 l min-1 (% end-tidal CO2 concentration)-1 with fatigue (P < 0.02).


The relationship between glucose-induced K+ATP channel closure and the rise in [Ca2+]i in single mouse pancreatic beta-cells. 1. Intracellular calcium [Ca2+]i and channel activity were simultaneously recorded in single, dissociated mouse beta-cells kept in culture for 1-3 days. [Ca2+]i was estimated from microfluorometric ratio methods using Indo-1. Channel activity was measured using the cell-attached configuration of the patch-clamp technique. 2. At low glucose concentrations (0.3 mM), resting K+ATP channel activity was prevalent. Increasing glucose up to 16 mM, produced a gradual decrease in K+ATP channel activity over a time course of 90-120 s (temperature = 23 degrees C) and an increase in [Ca2+]i. 3. In the majority of experiments, glucose elicited biphasic action currents (action potentials) which preceded the rise in [Ca2+]i. There was a close correlation between spike frequency and the levels of [Ca2+]i. 4. The sulphonylurea tolbutamide (1 mM) blocked K+ATP channels in 10-20 s. K+ATP channel blockade was associated with a quick rise in [Ca2+]i. 5. When K+ATP channel activity was stimulated in the presence of diazoxide (100 microM), increasing the glucose concentration from 3 to 16 mM produced a decrease in [Ca2+]i. Only when diazoxide was removed did glucose produce an increase in [Ca2+]i. 6. In a small population of cells, glucose (16 mM) produced a small decrease in K+ATP channel activity but not an increase in [Ca2+]i. In such cells, tolbutamide blocked K+ATP channels and produced an increase in [Ca2+]i. 7. These results demonstrate a close correlation between K+ATP channel activity and [Ca2+]i in beta-cells. The findings are consistent with the model in which glucose metabolism produces a rise in [Ca2+]i through the blockade of K+ATP channels, membrane depolarization and calcium current activation.


Crossed actions on group II-activated interneurones in the midlumbar segments of the cat spinal cord. 1. Evidence has been sought for crossed actions on midlumbar propriospinal neurones activated by ipsilateral group II muscle afferents, with particular emphasis on those neurones with projections to the ipsilateral hindlimb motor nuclei. 2. A large majority of group II-activated midlumbar neurones were influenced by stimulation of contralateral group II afferents. The most frequent and most powerful actions were from those nerves which most effectively influenced ipsilateral midlumbar neurones. Crossed actions from group I afferents were rare. 3. In the great majority of neurones the pattern of actions was similar from both limbs, the neurones being bilaterally excited, bilaterally inhibited or had both EPSPs and IPSPs from both sides. 4. The latencies of crossed actions suggest that the earliest crossed EPSPs from group II afferents were evoked disynaptically (i.e. via a single commissural neurone) and that the crossed IPSPs were evoked trisynaptically. 5. The pattern of crossed actions suggests a strong bilateral interaction between midlumbar neurones. The possible role of these neurones in postural control and the production of co-ordinated movements of the hindlimbs is discussed.


Coherence between the sympathetic drives to relaxed and contracting muscles of different limbs of human subjects. 1. This study was undertaken to quantify the simultaneous sympathetic drives to muscles in the two legs of human subjects, and to elucidate the extent to which a common drive determines sympathetic outflow to different limbs at rest, during apnoea and during voluntary contractions. 2. Sympathetic efferent activity was recorded simultaneously from fascicles of both peroneal nerves, innervating the pretibial flexor muscles. At rest the similarity was quantified for a sample of records by manual measurement of equivalent bursts in the two recordings, and for all records by cross-correlation and power spectral analysis of the two recordings. During contractions, only the latter method was used. 3. At rest the correlation coefficient for the relationship between the burst amplitudes for the two recordings was 0.72 (S.D. 0.1). For the same sequences, the computed coherence between the two recordings was 85.6% (S.D. 6.7%) at the cardiac period. There was a statistically significant linear relationship between these two measures of similarity, and this was stronger when data from sequences recorded during apnoea were included in the analysis. At rest the mean difference in coherence between consecutive sequences with no intervening manoeuvre (apnoea, contraction, change in recording site) was 4.2% (S.D. 4.3%). In only two of forty-nine such instances was the difference in coherence > 10%. 4. Apnoea at end-expiration increased the amplitude and frequency of sympathetic bursts and increased the similarity between the two recordings. The correlation coefficients increased from a mean of 0.72 at rest to 0.89 during apnoea. Coherence increased from a mean of 82.1% at rest to 91.9% during apnoea. 5. On the right side, graded voluntary contractions were performed at 5, 10, 20 or 30% maximal force using the muscle innervated by the fascicle from which the recording was made. The coherence between the recordings made from the right and left legs decreased by > 10% at each contraction level. Pooling the data for all contractions, there was a significant decrease in power at the cardiac frequency in the sympathetic recording from the contracting leg. Contraction of a synergist or antagonist at 10% maximum produced negligible changes in coherence. 6. It is concluded that, at rest, homologous muscles of the lower limbs are subject to a common drive and that, during apnoea, this common drive can dominate the sympathetic outflow to the virtual exclusion of regional drives. During voluntary activity, the importance of this common drive is lessened, presumably because of regionally specific changes involving the contracting muscle.(ABSTRACT TRUNCATED AT 400 WORDS)


Ca(2+)-dependent and -independent components of transmitter release at the frog neuromuscular junction. 1. When a Ca2+ chelator, bis (O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), was loaded into the presynaptic nerve terminal of the frog neuromuscular junction (NMJ), facilitation, measured as an increase in endplate potential (EPP) amplitudes during a train of ten stimulations at 100 Hz, was greatly decreased within 20 min of BAPTA-AM (the acetoxymethyl ester of BAPTA) perfusion, and remained at a constant low level thereafter, suggesting that [Ca2+]i at the presynaptic nerve terminal was buffered by BAPTA. 2. Detailed examination of the two components of facilitation of EPP amplitude in the BAPTA-loaded NMJs showed that the fast component was lost almost completely, while the slow component was unaffected by loaded BAPTA. Augmentation and potentiation were also unaffected by BAPTA. 3. Under external Ca(2+)-free conditions (with 1 mM-EGTA), both augmentation and potentiation of miniature endplate potential (MEPP) frequency were clearly observed after tetanic stimulation in the normal NMJ, and were also unaffected by loaded BAPTA. 4. The above findings strongly support the residual Ca2+ hypothesis for the fast component of facilitation, and suggest that the three slower processes (the slow component of facilitation, augmentation and potentiation) occur independently of [Ca2+]i. This Ca2+ independence was supported by the fact that facilitation and potentiation have multiplicative effects on the amount of release. 5. The quantal content of the first EPP in the train remained unchanged throughout the time course of BAPTA loading for most NMJs. This suggests that [Ca2+]i immediately adjacent to Ca2+ channels at the active zone triggers transmitter release and is little affected by loaded BAPTA. 6. MEPP frequency was almost unchanged during BAPTA loading, suggesting that the basal [Ca2+]i remained unchanged close to the dissociation constant of BAPTA for Ca2+ (108 nM). 7. The slow component of facilitation had a multiplicative relationship with augmentation and potentiation, suggesting that the underlying mechanism for the slow component of facilitation differs from that for augmentation and potentiation.


Equilibrium and kinetic study of glycine action on the N-methyl-D-aspartate receptor in cultured mouse brain neurons. 1. The characteristics of the activation of the N-methyl-D-aspartate (NMDA) response by glycine were studied using whole-cell and outside-out patch clamp recording techniques. 2. Glycine concentration-response (C-R) curves were measured in the presence of 10 microM-NMDA and fitted with the Hill equation modified to account for the response to NMDA observed in the absence of added glycine. The mean value of the apparent dissociation constant (KD) was 150 nM, and the mean value of the Hill coefficient (nH) was 1.1. When the KD was corrected for the concentration of contaminating glycine in nominally glycine-free solutions, estimated assuming that there is no response in the absence of glycine, the value was 130 nM. 3. The question of how many glycine binding sites there are on each NMDA receptor-channel complex was addressed by examining the curvature at the foot of the glycine C-R curve. An equation that allowed estimation of both the concentration of contaminating glycine and of the value of nH was fitted to glycine C-R data up to 50 nM. The mean value of nH was found to be 1.0, consistent with the idea that there is one glycine binding site. 4. The kinetics of the interaction of glycine with the NMDA receptor were measured by fitting single exponential curves to the current relaxation following a jump in glycine concentration in the presence of 10 microM-NMDA. The plot of the inverse of the relaxation time constant as a function of glycine concentration after the concentration jump was linear. The association rate constant was estimated from these data as 1.2 x 10(7) M-1 s-1 and the dissociation rate as 1.0 s-1. 5. Experiments were devised to allow the evaluation of the KD and dissociation rates of glycine in the absence of NMDA. They led to a value for KD of 80 nM, slightly but significantly lower than the value of 150 nM estimated in the presence of 10 microM-NMDA. The glycine dissociation rate in the absence of NMDA was found to be 0.7 s-1, not significantly different from that measured in the presence of 10 microM-NMDA. 6. The results are consistent with a model of the NMDA receptor with a single glycine binding site. The characteristics of glycine binding are similar in the absence and the presence of 10 microM-NMDA, although NMDA binding may cause a small increase in the glycine KD.(ABSTRACT TRUNCATED AT 250 WORDS)


Multiplicative and additive Ca(2+)-dependent components of facilitation at mouse endplates. 1. Facilitation of endplate potentials (EPPs) and frequency of miniature endplate potentials (MEPPs) were studied, in the presence of low Ca2+/raised Mg2+, in isolated mouse hemidiaphragm, using pseudo-random sequences of nerve stimulation and automated (computer) counting of MEPPs and quantal components of EPPs. 2. The facilitation in quantal content of EPPs (m) produced by one or more antecedent stimuli was accompanied by facilitation of MEPP frequency (fm) that was similar in magnitude and substantially less than expected if facilitation reflects persistent (residual) intraterminal Ca2+. The time course of 'phasic' quantal release, associated with the EPP, was little if at all altered with facilitation. 3. The magnitude and time course of facilitation was consistent with two distinct presynaptic processes, each manifest both in m and fm, (i) an effect to multiply transmitter release, and (ii) residual Ca2+ which adds to Ca2+ brought in by nerve impulses. These have distinct time courses. 4. After loading nerve terminals with bis (O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), facilitation of m and fm became very small. 5. At sufficiently low Ca2+/raised Mg2+ facilitation of m and fm became very small although latency histograms showed clear EPPs. However, the multiplicative component of facilitation became maximal at Ca2+/Mg2+ concentrations giving an average m value less than 0.1, corresponding to about 5% of normal Ca2+ entry per pulse. At lower Ca2+, facilitation was restored when EPPs were made larger using 4-aminopyridine. 6. With EPPs elicited by brief 'direct' nerve terminal depolarizations, facilitation was graded with pulse intensity (and m) and could be much less than with EPPs with similar m evoked by nerve stimuli at lower Ca2+ and/or higher Mg2+. 7. It was concluded that fast facilitation is primarily multiplicative and reflects activity within the nerve terminal of a Ca(2+)-sensitive process distinct from that generating Ca(2+)-dependent release.


Estimation of the carnosine content of different fibre types in the middle gluteal muscle of the thoroughbred horse. 1. Skeletal muscle samples were obtained by needle biopsy from one of two depths of the m. gluteus medius in a group of twenty race-trained thoroughbred horses. 2. The content of carnosine was determined in each muscle sample, part of which was used for histochemical analysis. Fibres were classified as type I, type IIA or type IIB on the basis of the pH dependent lability of the myosin ATPase reaction. 3. Muscle samples with a higher type II fibre section area (FSA) have a higher carnosine content than those with a higher type I FSA. 4. Multiple linear regression analysis was used to estimate the mean carnosine content of individual fibre types. The results estimated a mean carnosine content in type I fibres of 54 mmol (kg dry muscle (DM))-1, in type IIA fibres 85 mmol (kg DM)-1 and in type IIB fibres 180 mmol (kg DM)-1. 5. Based on the estimated values of single fibre carnosine content, there was close concordance between the estimated and the measured carnosine content of mixed fibre samples. 6. It would appear from this and other studies that carnosine has an important role as a physico-chemical buffer in equine middle gluteal muscle and that this is greatest in type IIB fibres, where it may account for up to 50% of physico-chemical buffering of H+ produced by muscle in the pH range 7.1-6.5.


Muscarine increases cation conductance and decreases potassium conductance in rat locus coeruleus neurones. 1. Whole-cell patch-clamp recordings were made from rat locus coeruleus neurones in slices of brain tissue in vitro. Muscarine (30 microM) caused an inward current of about 100 pA in neurones voltage clamped at -60 mV. 2. In about 75% of cells, the current elicited by muscarine was independent of potential in the range -60 to -120 mV and had no associated conductance change. 3. In about 25% of cells, the current became smaller with hyperpolarization, was associated with a decreased conductance, and reversed polarity between -100 and -140 mV. The reversal potential changed with the logarithm of the extracellular potassium concentration. Barium and caesium blocked inward rectification and also prevented reversal of the muscarine current. 4. When potassium ions of the intracellular and extracellular solutions were replaced by caesium, the current evoked by muscarine became smaller with depolarization at reversed polarity at +9 mV. This current was associated with an increase in conductance, and was greatly reduced when the extracellular sodium concentration was reduced to 20 mM. 5. The results could be quantitatively accounted for by a model in which muscarine both increases a voltage-independent cation conductance and decreases the inward rectifier potassium conductance.


Effect of maternal cold exposure on brown adipose tissue and thermogenesis in the neonatal lamb. 1. This study examines the effect of chronic cold exposure during pregnancy, induced by winter shearing twin-bearing ewes 4 weeks before predicted lambing date, on O2 consumption and CO2 production during non-rapid-eye-movement (REM) sleep in lambs maintained for at least 1 h at warm (28-18 degrees C) and cold (14-5 degrees C) ambient temperatures at 1, 4, 14 and 30 days of age. This was combined with measurement of the thermogenic activity (GDP binding to uncoupling protein in mitochondrial preparations) of perirenal adipose tissue from lambs immediately after birth and at 33 days of age. 2. Lambs born from shorn (cold-exposed) ewes were 15% heavier (P < 0.01) and possessed 21% (P < 0.01) more perirenal adipose tissue that contained 40% more protein and mitochondrial protein than unshorn (P < 0.05) controls. Total GDP binding in perirenal adipose tissue was 40% greater (P < 0.05) in lambs born from shorn ewes but there was no difference in lipid content of this tissue between the two groups. 3. At 1 day of age, lambs born from shorn ewes exhibited a 16% higher (P < 0.05) rate of O2 consumption (per kilogram bodyweight) at the warm temperature and a 40% greater metabolic response to the cold ambient temperature. All lambs born from shorn ewes responded to cold exposure without shivering (i.e. via non-shivering thermogenesis) whilst shivering was measured in four out of seven lambs in the unshorn group. These differences had disappeared by 4 days of age as a result of a 25% increased (P < 0.01) rate of O2 consumption in the warm in lambs born from unshorn ewes and a 20% decrease (P < 0.05) in the response to the cold in lambs from shorn ewes. Shivering during cold exposure was measured in six out of nine lambs born from shorn ewes indicating a rapid alteration in thermoregulatory responses to cold during the first few days of life. 4. The levels of GDP binding and mitochondrial protein in perirenal adipose tissue fell by one-third in both groups of lambs during the first 33 days of life whereas lipid content either increased or was unchanged. This indicated that brown adipose tissue (BAT) was developing the characteristics of white adipose tissue.(ABSTRACT TRUNCATED AT 400 WORDS)


Ca2+ efflux mechanisms following depolarization evoked calcium transients in cultured rat sensory neurones. 1. We have used a combination of microfluorimetry and patch-clamp techniques to investigate cytoplasmic Ca2+ ([Ca2+]i) buffering in response to physiological Ca2+ loads in neurones cultured from the dorsal root ganglia of the rat. 2. In cells loaded with Indo-1 AM and using high resistance microelectrodes to initiate and record action potentials, single action potentials were associated with a measurable rise in [Ca2+]i. Short trains of action potentials evoked [Ca2+]i transients with monoexponential recovery rates with time constants of around 5 s. 3. Similar Ca2+ buffering properties were seen in cells perfused with patch-clamp pipettes in the whole-cell recording mode suggesting that the slow (seconds) Ca2+ buffering properties were not seriously perturbed by the recording technique. 4. In cells held under voltage clamp, reversal of the Na(+)-Ca2+ exchanger driving force had a small but significant effect on the rate of Ca2+ removal. 5. Increasing extracellular pH or adding vanadate (200 microM) to the internal solution dramatically slowed the rate of recovery. Addition of calmidazolium to the pipette solution also produced a significant but much less dramatic slowing of Ca2+ efflux. 6. The results demonstrate that the activity of a plasmalemmal Ca(2+)-ATPase is important for the removal of somatic Ca2+ loads of a similar amplitude to those generated by the firing of a few action potentials.


Phenylephrine-induced translocation of protein kinase C and shortening of two types of vascular cells of the ferret. 1. The relationship between phenylephrine-induced smooth muscle contraction and the subcellular distribution of protein kinase C (PKC) was investigated. 2. Cell shortening induced by phenylephrine (10(-5) M) was measured in single vascular cells freshly isolated from ferret portal vein and aorta. 3. At various time points during phenylephrine activation, single cells were fixed with paraformaldehyde and the distribution of PKC was imaged in cells labelled with the fluorescent PKC probe 12-(1,3,5,7-tetramethylBODIPY-2-propionyl)phorbol-13-acetate. 4. The PKC probe located to a perinuclear region, the cytosol and surface membrane. The amplitude and time course of the phenylephrine-induced changes in the surface membrane/cytosol fluorescence ratio were measured and compared with the amplitude and time course of phenylephrine-induced cell shortening. 5. In portal vein cells incubated in 1 mM-external Ca2+, phenylephrine caused significant shortening and time-dependent translocation of the PKC probe to the surface membrane, but cell shortening preceded PKC translocation. In Ca2+free solution both cell shortening and translocation of the probe were completely inhibited. 6. Verapamil (3 x 10(-7) M) partially, but significantly, inhibited the magnitude of cell shortening and delayed the onset and time to peak shortening. Translocation of PKC in verapamil preceded or coincided with cell shortening. 7. In aorta cells incubated in 1 mM-extracellular Ca2+, phenylephrine induced significant shortening and time-dependent translocation of the PKC probe. Cell shortening preceded PKC translocation. In Ca(2+)-free solution, shortening was only partially, but significantly, inhibited and PKC translocation preceded the fraction of the shortening response that remained. 8. These data are consistent with a role for PKC in the maintenance of the phenylephrine-induced contraction in both portal vein and aorta. The data also suggest that phenylephrine-induced contraction may involve activation of a Ca(2+)-dependent PKC isoform in ferret portal vein but a Ca(2+)-independent isoform in ferret aorta.


Calcium-activated potassium channels in native endothelial cells from rabbit aorta: conductance, Ca2+ sensitivity and block. 1. Isolated native endothelial cells, obtained by treatment of rabbit aortic endothelium with papain and dithiothreitol, were voltage clamped, and single channel (unitary) and spontaneous transient outward currents (STOCs) were recorded from both whole cells and excised membrane patches. 2. In inside-out patches, the reversal potential of unitary currents was dependent on the extracellular K+ concentration and had a single-channel slope conductance of 220 pS in symmetrical 140 mM-K+ solutions. The open-state probability (Po) of the unitary K+ currents was sensitive to the intracellular Ca2+ concentration with half-maximal activation at approximately 1 microM at +20 mV. The ionic selectivity and Ca2+ sensitivity indicate that a large conductance, Ca(2+)-activated K+ channel is present in freshly dissociated rabbit aortic endothelial cells. 3. The frequency and amplitude of whole-cell unitary currents and amplitude of spontaneous transient outward currents were voltage-dependent. Whole-cell outward K+ currents evoked by depolarizing voltage ramps had amplitudes often corresponding to the simultaneous opening of more than five single Ca(2+)-activated K+ channels. Lowering the intracellular EGTA concentration tenfold, and hence the Ca2+ buffering capacity of the cell, increased unitary K+ current activity and shifted the relationship between Po and membrane potential by approximately -20 mV. 4. Bradykinin (1 microM), adenosine 5'-triphosphate (3 microM) and acetylcholine (3 microM) applied extracellularly evoked a biphasic increase in N Po (where N is number of channels activated) of the Ca(2+)-activated K+ channel studied in the whole-cell recording configuration. The development of a biphasic response to agonist stimulation requires a source of extracellular Ca2+. The sustained increase in N Po of the Ca(2+)-activated K+ channel was attenuated upon the removal of external Ca2+ (Mg2+ replacement) or in the presence of the Ca2+ entry blocker, Ni2+, and the potassium channel blockers tetrabutylammonium (TBA) or tetraethylammonium (TEA). 5. Unitary and spontaneous transient outward currents were inhibited by extracellularly applied TEA (0.5 mM), TBA (0.5-5 mM) and charybdotoxin (100 nM). Ca(2+)-activated K+ currents were blocked completely by 5 mM-TEA, whereas 3,4-diaminopyridine (1 mM), Ba2+ (10 mM) and apamin (0.1-1 microM) did not abolish these K+ currents. 6. The K+ channel opener cromakalim (10 microM) evoked a sustained increase in N Po of the Ca(2+)-activated K+ channels which was not potentiated by the addition of bradykinin. Glibenclamide (10 microM) alone increased N Po and partially inhibited the cromakalim-induced increase in N Po with respect to control.(ABSTRACT TRUNCATED AT 400 WORDS)


Luminal Ca2+ promoting spontaneous Ca2+ release from inositol trisphosphate-sensitive stores in rat hepatocytes. 1. Spontaneous Ca2+ release from the inositol 1,4,5-trisphosphate (InsP3)-sensitive stores in permeabilized hepatocytes was monitored using Fluo-3 to measure the free [Ca2+] of the medium bathing the cells. 2. Permeabilized cells rapidly sequestered Ca2+, reducing the [Ca2+] to 103 +/- 5 nM. Under conditions that depended critically upon cell density and the amount of Ca2+ in the medium, this was followed by a slow increase in [Ca2+] culminating in a substantial Ca2+ spike representing synchronous discharge from the InsP3-sensitive stores. 3. During the latency preceding the Ca2+ spike, the stores increased their sensitivity to InsP3. This sensitization seemed to be an all-or-none phenomenon. 4. Oxidized glutathione and thimerosal promoted the spontaneous release by sensitizing the InsP3 receptor. 5. An increase in the [Ca2+] within the stores was required for both the increased sensitivity to InsP3 and the subsequent spike. 6. Caffeine (6 mM) antagonized the effect of very low InsP3 concentrations and abolished the Ca2+ spike, without itself releasing Ca2+. 7. Our results suggesting that luminal Ca2+ may sensitive InsP3-sensitive stores leading to spontaneous Ca2+ mobilization will be discussed in the light of a modified version of the two-pool model for explaining cytosolic Ca2+ oscillations.


Monosynaptic EPSPs elicited by single interneurones and spindle afferents in trigeminal motoneurones of anaesthetized rats. 1. Our aim has been to quantify the monosynaptic connections of trigeminal interneurones and spindle afferents onto jaw-elevator motoneurones as a step towards identifying common features in organization of monosynaptic inputs onto motoneurones. We have used the intracellular variant of the spike-triggered averaging method to examine the connections of single identified trigeminal interneurones and jaw-elevator muscle spindle afferents onto single jaw-elevator motoneurones. The interneurones examined lay in the region immediately caudal to the trigeminal motor nucleus. The experiments were performed on rats anaesthetized with pentobarbitone, paralysed and artificially ventilated. 2. Ten EPSPs and eight IPSPs were obtained from examining the connections of seventeen interneurones to thirty-six motoneurones, suggesting a functional connectivity of 50% for individual interneurones onto elevator motoneurones. Fourteen EPSPs were obtained from examining the connections of thirteen spindle afferents onto twenty-seven motoneurones, giving a functional connectivity of 52% for individual spindle afferents onto elevator motoneurones. The amplitudes of the EPSPs elicited by interneurones ranged from 7-48 microV (mean = 17, S.D. = 12.5, n = 10) and from 7 to 289 microV (mean = 64, S.D. = 76.0, n = 14) for the spindle-mediated EPSPs; the difference in the two means was not significant (P = 0.07). 3. However, the amplitude of averaged responses obtained by signal averaging methods are dependent on the assumption that the postsynaptic response occurs following every impulse in the presynaptic neurone. We therefore estimated the percentage of sweeps which contained EPSPs triggered by the presynaptic neurone under study. In essence the method used consisted of visual inspection of the individual sweeps comprising an average in order to assess the occurrence of EPSPs within six separate time windows, each of duration +/- 0.3 ms. Five windows were placed at randomly selected times on average and were used to provide an estimate of the frequency of occurrence of randomly triggered EPSPs. The sixth window was centred on the start of the averaged EPSP and the frequency of occurrence of randomly triggered EPSPs was subtracted from the frequency of occurrence of EPSPs in this window to produce an estimate of the incidence of EPSPs triggered by the presynaptic neurone under study. 4. Values of the incidence of occurrence of EPSPs triggered by the presynaptic neurones ranged from 4.3 to 92% for the fifteen averaged EPSPs which could be analysed in this manner (two elicited by interneurones and thirteen by spindle afferents).(ABSTRACT TRUNCATED AT 400 WORDS)


Ca(2+)-dependent heat production under basal and near-basal conditions in the mouse soleus muscle. 1. The rate of energy expended for the clearance of sarcoplasmic Ca2+ by sarcoreticular Ca2+ uptake process(es), plus the concomitant metabolic reactions, was evaluated from measurements of resting heat production by mouse soleus muscle before and after indirect inhibition of Ca2+ uptake by sarcoplasmic reticulum (SR). 2. Direct inhibition of the Ca2+, Mg(2+)-ATPase of SR membrane in intact muscle preparations exposed to the specific inhibitor 2,5-di(tert-butyl-1,4-benzohydroquinone (tBuBHQ) slowly increased the rate of heat production (E). Indirect inhibition of SR Ca2+ uptake was obtained by reducing sarcoplasmic Ca2+ concentration (Ca2+i) as a consequence of reducing Ca2+ release from the SR using dantrolene sodium. This promptly decreased E by 12%. Exposure of the preparations to an Mg(2+)-enriched environment (high Mg2+) or to the chemical phosphatase 2,3-butanedione monoxime (BDM), two other procedures aimed at decreasing SR Ca2+ release, also acutely decreased E, by 20 and 24%, respectively. 3. Subthreshold-for-contracture depolarization of the sarcolemma achieved by increasing extracellular K+ concentration to 11.8 mM induced a biphasic increase of E: an initial peak to 290% of basal E, followed by a plateau phase at 140% of basal E during which resting muscle tension was increased by less than 3%. Most, if not all, of the plateau-phase metabolic response was quickly suppressed by dantrolene or high Mg2+ or BDM. Another means of increasing SR Ca2+ cycling was to partially remove the calmodulin-dependent control of SR Ca2+ release using the calmodulin inhibitor W-7. The progressive increase in E with 30 microM-W-7 was largely reduced by dantrolene or high Mg2+ or BDM. 4. In the presence of either dantrolene or BDM to prevent the effect of W-7 on SR Ca2+ release, exposure of the muscle to W-7 acutely suppressed about 3% of E. This and the above results confirm that the plasmalemmal, calmodulin-dependent Ca(2+)-ATPase, although a qualitatively essential part of the Ca2+i homeostatic system of the cell, can only be responsible for a very minor part of the energy expenditure devoted to the homeostasis of Ca2+i. Active Ca2+ uptake by SR which, at least in the submicromolar range of Ca2+i, is expected to be responsible for most of this Ca(2+)-dependent energy expenditure, might dissipate up to 25-40% of total metabolic energy in the intact mouse soleus under basal and near-basal conditions.


Regulation of perfusive O2 transport during exercise in humans: effects of changes in haemoglobin concentration. 1. Recently it was suggested that submaximal cardiac output (Q) could vary in response to changes in arterial O2 concentration (Ca,O2), so that arterial O2 delivery (Qa,O2 = Q x Ca,O2, in ml min-1) is kept constant. 2. This hypothesis was tested on eight healthy male subjects, at rest and during exercise (50, 100 and 150 W) in three conditions: normaemia (N), after 6 weeks of endurance training (T), and 2 days after subsequent autologous blood reinfusion (P). 3. Measured variables were oxygen consumption (VO2), by open circuit method, Q, by a CO2 rebreathing method, and haemoglobin concentration ([Hb]), by a photometric method. Ca,O2 was calculated as the product of [Hb], arterial O2 saturation (0.97), and the O2 binding coefficient. 4. [Hb] and thus Ca,O2 increased by 2.6% (T vs. N) and subsequently by further 5.8% (P vs. T). VO2 and Qa,O2 were linear functions of power (w), both relationships being unaffected by changes in Ca,O2. As a consequence, the linear Q vs. VO2 relationships were shifted downward as Ca,O2 increased. 5. The VO2 vs. w and the Qa,O2 vs. w relationships had the same slope. Therefore, the difference between Qa,O2 (w) and VO2 (w), equal to O2 flow in mixed venous blood (Qv,O2), was constant. 6. In conclusion, the tested hypothesis was supported by the present results. The observed constancy of Qv,O2 suggested that Qv,O2 may play a key role in regulating the cardiovascular response to exercise.


Primary effects of carotid chemoreceptor stimulation on gracilis muscle and renal blood flow and renal function in dogs. 1. In chloralose-anaesthetized and artificially ventilated dogs, the carotid sinus regions were vascularly isolated and perfused either with arterial or mixed (arterial and venous) blood (partial pressure of O2 (PO2) 43.8 +/- 2.4 mmHg, mean +/- S.E.M. n = 14) to stimulate the carotid chemoreceptors. The carotid sinus pressure was held constant at 142.0 +/- 2.8 mmHg. Measurements were made of renal and gracilis muscle blood flow by wrap-round electromagnetic flow probes placed around the renal and gracilis arteries, glomerular filtration rate by creatine clearance, urinary sodium excretion by flame photometry and solute excretion by osmometry. 2. In ten dogs, with intact cervical vagosympathetic trunks, carotid chemoreceptor stimulation produced significant increases in aortic pressure (AoP) of 12.7 +/- 1.1% (n = 10, P < 0.001), in glomerular filtration rate (GFR) of 14.7 +/- 4.1% (P < 0.001), urine flow rate (V) of 16.5 +/- 3.5% (P < 0.002), in urinary sodium excretion (UNaV) of 17.5 +/- 2.5% (P < 0.005) and in urinary osmolar excretion (UosmV) of 13.2 +/- 2.2% (P < 0.001), but a significant decrease in renal blood flow (RBF) of 5.8 +/- 1.8% (P < 0.02). In six of these dogs in which gracilis muscle blood flow (MBF) was also recorded, carotid chemoreceptor stimulation caused significant increases in AoP of 12.8 +/- 1.4% (n = 6, P < 0.001) and in MBF of 10.0 +/- 1.6% (P < 0.002), and a small but significant decrease in RBF of 3.6 +/- 1.5% (P < 0.02). 3. In fourteen dogs, with sectioned cervical vagosympathetic trunks, carotid chemoreceptor stimulation produced increases in AoP of 22.0 +/- 2.6% (n = 14, P < 0.001), in GFR of 36.9 +/- 4.2% (P < 0.001), in V of 30.1 +/- 4.4% (P < 0.001), in UNaV of 31.4 +/- 5.3% (P < 0.001), and in UosmV of 25.7 +/- 5.8% (P < 0.001). However, it produced a greater decrease in RBF of 10.5 +/- 1.9% (P < 0.001). In ten of these dogs, where MBF was recorded, carotid chemoreceptor stimulation caused greater increase in AoP of 22.4 +/- 3.0% (n = 10, P < 0.001) and in MBF of 32.8 +/- 3.7% (P < 0.001), and a greater decrease in RBF of 9.8 +/- 1.9% (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)


Ionic basis of membrane potential changes induced by anoxia in rat dorsal vagal motoneurones. 1. The effects of anoxia on membrane properties of 119 dorsal vagal motoneurones (DVMs) were investigated in an in vitro slice preparation of the rat medulla. 2. Membrane potential was unaffected by anoxia in 11% of DVMs. An hyperpolarization accompanied by a decrease in input resistance occurred in 44% of DVMs; the remaining 45% depolarized with either an increase (60%) or decrease in input resistance (40%). TTX at a concentration of 0.3-1 microM did not significantly affect these responses. 3. Anoxic artificial cerebrospinal fluid (ACSF) containing 20 mM-TEA reversed the response of DVMs that hyperpolarized in standard ACSF to reveal a depolarization of 7.4 +/- 2.1 mV, and increased the anoxic depolarization from 5.0 +/- 0.7 to 8.7 +/- 1.4 mV. 4. Anoxic depolarization was converted to an hyperpolarization of 7.3 +/- 2.1 mV in ACSF containing 5 mM-4-aminopyridine (4-AP) and 1 microM-TTX. A residual depolarization of 4.5 +/- 3.5 mV was then observed in ACSF containing 5 mM-4-AP, 1 microM-TTX and 20 mM-TEA. Anoxic hyperpolarization was increased from 7.8 +/- 1.8 to 10.0 +/- 3.9 mV in 5 mM-4-AP and 1 microM-TTX and converted to a depolarization of 5.3 +/- 4.5 mV in 5 mM-4-AP, 1 microM-TTX and 20 mM-TEA. 5. In anoxic ACSF containing TEA, the action potential width was increased from 0.92 +/- 0.04 to 8.1 +/- 1.1 ms in hyperpolarizing DVMs, and from 0.85 +/- 0.01 to 2.4 +/- 1.0 ms in depolarizing DVMs. The increase in width was prevented by 2-3 mM-Mn2+. 6. The long after-hyperpolarization (AHP) of DVMs, which is contributed to by both an apamin-sensitive IK(Ca) and an apamin, charybdotoxin and TEA insensitive IK(Ca) was decreased in duration from 2.59 +/- 0.14 to 1.94 +/- 0.12 s during anoxia. 7. It is concluded that anoxia enhances the delayed rectifier current (IK(DR)) and an inward current, probably ICa, but suppresses the A currents (IA). In DVMs that hyperpolarize during anoxia, the increase in IK(DR) outweighs the increase in ICa and the decrease in IA. In depolarizing DVMs the decrease in IA and increase in ICa outweight the increase in IK(DR). The change in input resistance is determined by the relative sizes of current enhancement or suppression.


Prognostic indicators for horses with duodenitis-proximal jejunitis. 75 horses (1985-1989). The medical records of 75 horses with duodenitis-proximal jejunitis (DPJ) were reviewed. Ages, physical parameters, laboratory values, and treatment data were compared between horses surviving DPJ and horses not surviving DPJ (Table 1). Fifty of 75 horses (66.6%) survived. Sixty-six horses (88.0%) were managed with medical treatment alone and nine horses (12.0%) were managed with medical treatment plus surgical intervention. Using a logistic regression model, the association of each of the 19 physical and laboratory parameters with death was evaluated retrospectively in the 75 horses. Three parameters (anion gap, abdominal fluid total protein concentration, and volume of gastric fluid for the first 24 hours of hospitalization) were significantly associated with death by univariate analysis. Using a stepwise multiple logistic regression, two parameters remained significantly associated with death (P < 0.05), anion gap and abdominal fluid total protein concentration.


Lymphedema. Clinical signs, diagnosis, and treatment. Medical management of lymphedema is warranted in all dogs with suspected congenital lymphedema, before surgical intervention. Although pharmaceutical agents, such as the benzo-pyrones, have not been investigated for clinical use in dogs, such studies appear to be justified. None of the surgical techniques discussed will cure lymphedema. The only technique reported with any frequency in the dog has been excision of affected tissues, and although some successes have been reported with this procedure, others have found it to be of no benefit or severe complications have occurred. Excisional techniques require meticulous attention to prevent infection intraoperatively and postoperatively. Staging the procedure may decrease problems associated with devascularization of remaining tissues. Evaluation of other techniques may be warranted in dogs; however, no technique has proven to be consistently beneficial in human beings with lymphedema.


High-resolution imaging of chromosome-related structures by atomic force microscopy. An atomic force microscope (AFM) was combined with a conventional optical microscope. The optical microscope proved to be very convenient for locating objects of interest. In addition, the high-resolution AFM image can be compared directly with the traditional optical image. The instrument was used to study chromosome structures. High-resolution chromosome images revealed details of the 30-nm chromatide structure, confirming earlier electron microscopic observations. Chromosomes treated with trypsin revealed a banding pattern in height which is very similar to the optical image observed after staining with Giemsa. Furthermore, it is shown that the AFM can be used to locate DNA probes on in situ hybridized chromosomes. Images of the synaptonemal complex isolated from rat spermatocytes revealed details that improve the understanding of the three-dimensional structure of this protein.


Low-energy electron microscopy (LEEM) and mirror electron microscopy (MEM) of biological specimens: preliminary results with a novel beam separating system. Low-energy electron microscopy (LEEM) and mirror electron microscopy (MEM) utilize a parallel beam of slow-moving electrons backscattered from the specimen surface to form an image. If the electrons strike the surface an LEEM image is produced and if they are turned back just before reaching the surface an MEM image results. The applications thus far have been in surface physics. In the present study, applications of LEEM and MEM in the biological sciences are discussed. The preliminary results demonstrate the feasibility of forming images of uncoated cultured cells and cellular components using electrons in the threshold region (i.e. 0-10 V). The results also constitute a successful test of a novel beam-separating system for LEEM and MEM.


Increased serum growth hormone concentration in feline hypertrophic cardiomyopathy. Serum growth hormone concentration was measured by radioimmunoassay in 31 cats with hypertrophic cardiomyopathy, 38 normal cats, and 35 cats with other cardiac disease. Cats with hypertrophic cardiomyopathy had a significantly increased serum growth hormone concentration when compared with normal cats and cats with other cardiac disease. The serum growth hormone concentration in cats with hypertrophic cardiomyopathy was less than that previously reported in cats with growth hormone secreting pituitary tumors. Pituitary tumors were not identified in eight of the cats with hypertrophic cardiomyopathy examined at necropsy. An increased serum growth hormone concentration may be measured in cats with hypertrophic cardiomyopathy but it is unclear if the increased serum growth hormone concentration is a cause or effect of hypertrophic cardiomyopathy.