Peripheral sensilla of some lower invertebrates: the Platyhelminthes and Nematoda.

The flatworms (Platyhelminthes) and the round worms (Nematoda) are phyla exhibiting strikingly different levels of cellular organization. In both, sensilla are composed of the endings of sensory dendrites intercalated into their epidermis. In flatworms, sensilla that penetrate the syncytial epidermis bear sensory processes derived from cilia. In free-living species, the sensory processes more closely resemble motile cilia, while in parasites, greater deviations occur from the classical cilium pattern. Estimates of the function of the various sensilla have been largely arbitrary, and remain based on ultrastructural features. Sensilla in round worms lie below or within a heavy secreted cuticle. Two glia-like cell types occur. The socket cell mediates contact with cuticle and is responsible for cuticular modifications essential for operation of the sensillum. The sheath cell forms a receptor cavity around the sensory processes and regulates its environment. Sensory processes vary greatly from the classical cilium pattern. Absence of a basal body, but preservation of a ciliary necklace, suggests that the latter has a primary importance in sensory transduction. Estimates of function are based largely on ultrastructural features and analogies to arthropod sensilla. Genetic studies with the free-living nematode Caenorhabditis are beginning to demonstrate details of function and development. Speculations on the roles of basal bodies, rootlets, and vesicles and on the significance of recessed sensilla are given.


Preparation of TEM foils from Nb-10 a/o Si.

Ductile phase toughened composites contain phases with significantly different physical properties. Consequently, these phases thin at different rates depending on the sample preparation procedure. A new TEM foil preparation method for the ductile phase toughened Nb-10 a/o Si material has been developed. The method involves chemical thinning in a 70% nitric acid/30% hydrofluoric acid solution followed by electropolishing in a 12.5% sulfuric acid/87.5% methanol electrolyte at -40 degrees C. This procedure for making TEM foils results in large thin areas with the minimum of artifacts. Mechanical grinding of a sample followed by either ion milling, dimpling, or electropolishing produced foils with large electron transparent areas, but with uncharacteristic features of the original Nb-10 a/o Si alloy microstructure. These artifacts were identified as dislocations, surface mottling, and antiphase domains.


In situ freeze-fracture of monolayer cell cultures grown on a permeable support.

The growth of cultured epithelial cells on permeable supports allows increased cell differentiation and the assessment of a variety of transcellular and paracellular transport processes. The need to assess the corresponding ultrastructural characteristics of these cells under identical conditions prompted this laboratory to develop a reliable method for producing freeze-fracture replicas of these cultures. Sections of filter inserts with the cell-side facing up are placed between layers of polyvinyl alcohol with a strip of mylar positioned on the layer of polyvinyl alcohol. Following freezing, the monolayer is fractured by lifting the mylar strip from the assembly. The result is a consistent fracture of the apical membrane sufficient for analysis of tight junction sealing strands, microvilli distribution, and intramembranous particle (IMP) distribution between apical and lateral membrane domains. This method utilizes standard equipment and readily available materials and, most importantly, allows the freeze-fracture and replication of an undisturbed cell monolayer.


Role for the submandibular gland in modulating pulmonary inflammation following induction of systemic anaphylaxis.

Previous studies have shown that bilateral decentralization of the superior cervical ganglia (SCG; decentralization) attenuates allergen-induced pulmonary inflammatory responses in male rats sensitized to the nematode Nippostrongylus brasiliensis. The present report examines the neuronal and glandular mechanisms mediating the protection against pulmonary inflammation afforded by decentralization. Tissues and organs innervated by the SCG are responsible for this protection since, in a manner similar to decentralization, bilateral removal of the SCG (ganglionectomy) reduced anaphylaxis-induced accumulation of inflammatory cells in bronchoalveolar lavage fluid. Removal of the submandibular gland (sialadenectomy) did not modify the severity of the pulmonary inflammation, but concurrent sialadenectomy and decentralization abolished the protective effect of decentralization. Thus, we postulate that cervical sympathetic nerves tonically inhibit release of anti-inflammatory factors from submandibular glands. No relationship was found between noradrenaline and serotonin content of submandibular glands and the degree of protection against pulmonary inflammation offered by decentralization and ganglionectomy. Both decentralization and ganglionectomy appeared to increase the level of transcripts that encode immunomodulatory growth factors (nerve growth factor and epidermal growth factor) in submandibular glands, but these denervations evidently did not modify the transcripts for TGF beta 2. Systemic inflammatory events are regulated by the central nervous system at a level superior to the SCG probably through modulation of immunoregulatory factors in submandibular glands.


Modulation of human natural killer cell activity by exposure to uncontrollable stress.

Changes in natural killer cell (NK) activity and proportions of circulating T and NK lymphocyte subsets were assessed in adult males immediately after exposure to controllable or uncontrollable stress (noise) as well as 24 and 72 h later, in order to track the time course of the effects of stress. The role of control-relevant personality variables as moderators of the stress-immunosuppression relationship was considered. Subjects who perceived they had control over the noise as well as no-noise "control" subjects showed no reduction in NK activity. By contrast, subjects who perceived that they had no control over the stressor showed reduced NK activity immediately after the conclusion of the first 20-min stress session, and the reduced NK activity was found as long as 72 h later. Optimism and one's desire to be in control enhanced the negative impact of uncontrollable noise on NK activity. No differences between conditions were found on number of NK cells or a variety of T cell subsets. The results suggest the importance of perceived control in moderating the short- and long-term effects of stress on NK activity.


Neuro-hormonal host defence in endotoxin shock.

The sensitivity (LD100) of mice to lipopolysaccharide (LPS) endotoxin and to its toxic moiety, lipid A (LA), increased 500-fold after adrenalectomy (ADX). Inhibition of glucocorticoid synthesis in intact mice by metyrapone had a similar, though less dramatic, sensitizing effect to LPS. In ADX mice, the serum level of tumor necrosis factor-alpha (TNF) was 40-60 times higher than that in controls at 2 h after LPS/LA treatment. In intact mice the serum corticosterone level fell 1 h after lipid A injection to below detectable levels, which was followed by a brisk increase reaching the peak level of 48-50 micrograms/100 ml at 2 h. Both TNF production and the lethal effect of PLS/LA could be inhibited in ADX mice by glucocorticoid treatment. Plasma prolactin was increased significantly 1 h after endotoxin administration in both intact and ADX animals.


Stress-induced alterations in interferon production and class II histocompatibility antigen expression.

Mild electric foot-shock has been shown to be a stressor that can alter immune responses. Male Lewis rats were exposed to one session of 16 5.0-s 1.6-mA foot-shocks. Production of interferon-gamma by splenocytes in response to concanavalin-A was decreased in spleens from the shocked rats compared to control spleens. Spleen cells from rats treated with nadolol, a peripherally acting beta-adrenergic receptor antagonist, and then shocked, showed dose-dependent attenuation of the suppression of interferon-gamma production. This suggests that catecholamines mediate shock-induced suppression of interferon-gamma production. The percentage of splenic mononuclear cells expressing class II histocompatibility (Ia) antigens on their surfaces from spleens of shocked rats was determined by flow cytometry. Significantly decreased class II positive mononuclear cells were present in the spleens of shocked rats in comparison to the spleens of control rats. This may reflect an alteration of cell trafficking or decreased production of class II antigens.


Removal from natal social group to peer housing affects cortisol levels and absolute numbers of T cell subsets in juvenile rhesus monkeys.

Psychosocial stress associated with the removal of six naive juvenile rhesus monkeys from their natal social group to peer housing resulted in increased basal cortisol secretion and significant decrements in the absolute numbers of the T lymphocyte subsets in the peripheral blood. Six subjects matched for age and social rank remained in the group of 80 animals serving as controls. Baseline immune and cortisol measurements were obtained before the six test subjects were removed from the group and housed together in an outdoor circular enclosure. Blood samples were taken 24 h following removal of the test subjects from the group and at intervals thereafter through 11 weeks. Compared to controls, test subjects showed a significant decrease in the absolute numbers of CD4+ (-56.9%) and CD8+ T cells (-57.6%) and a significant increase in basal cortisol levels (+43.9%) 24 h following removal to peer housing. Group difference in the absolute numbers of most immune cells persisted through 11 weeks, whereas cortisol differences lasted only through 2 weeks. These data, when compared to an earlier study employing an identical protocol, with the exception that subjects were housed in indoor individual cages following separation, fail to demonstrate a modulating effect of randomly chosen peer-mates on the stress effects produced by social separation.


Central nervous system influences on lymphocyte migration.

The immune response network is only one of many physiologic adaptive responses to environmental change and there is now substantial evidence that adaptive responses involving the central nervous system have an impact on immune outcome. Effective immune function depends upon a highly mobile population of precursor and effector cells of the lymphoid system. In this review it is proposed that many of the alterations in immunity resulting from CNS activity may be explained in terms of changes in lymphocyte migration patterns in response to endocrine signals, neural signals via neurotransmitter release, or direct contacts between nerves and cells of the immune system.


What differentiates antiestrogen-liganded vs estradiol-liganded estrogen receptor action?

This paper provides an annotated summary of the current literature detailing what is known about the interaction of antiestrogen-liganded estrogen receptor (ER) vs estradiol-liganded ER with DNA in vitro and in vivo. It describes the current models of the mechanism by which antiestrogen-liganded ER blocks transcription of certain estrogen-regulated genes.


Gene amplification as a target for cancer chemotherapy.

Facile gene amplification is one aspect of the genetic instability associated with transformed cells. Amplification of oncogenes and proto-oncogenes contributes to carcinogenesis and tumor progression. Gene amplification is also a common basis for resistance to anticancer drugs. The observation that low level cytotoxic stress can cause rapid loss of amplified genes from cultured cell populations suggests that gene amplification may be a potential target for cancer chemotherapy. Drug-induced loss of amplified genes is seen with a wide variety of extrachromosomally amplified genes, including drug resistance genes and proto-oncogenes. A number of drugs and differentiating agents have been reported to cause rapid loss of unstably amplified genes. An effect on amplified genes or cells carrying amplified genes may contribute to the selective action of drugs presently used for cancer chemotherapy. A better understanding of drug-induced amplified gene loss may lead to new strategies for cancer treatment.


Effect of 2',2'-difluorodeoxycytidine on the viability and radiosensitivity of EMT6 cells in vitro.

EMT6 mouse mammary tumor cells were used to examine the cytotoxic effects of 2',2'-difluorodeoxycytidine (gemcitabine; dFdC) alone and in combination with radiation. The cytotoxicity of dFdC differed from that of most antimetabolites. The concentration-response curve for exponentially growing cells treated for 4 hr with various drug concentrations was exponential down to a surviving fraction of 0.05; thus, dFdC appeared to kill cells in all phases of the cell cycle, rather than killing only the S-phase cells that compose approximately 50% of the cell population. High concentrations of dFdC were toxic to cells in plateau phase EMT6 cultures, as well as to cells in rapidly proliferating cultures. These findings are thought to reflect the unusual cellular pharmacokinetics of the compound. Treatment of exponentially growing cultures with dFdC before, during, and after irradiation was extremely effective in killing the cells; the survival curves for cells treated with drug plus radiation were statistically compatible with either additive cytotoxicity or a synergistic effect (i.e., radiosensitization by dFdC). These studies also provided evidence that dFdC released by dying cells could produce delayed cytotoxic effects on cells not treated directly with dFdC. These data provide several bases for expecting beneficial therapeutic effects from antineoplastic regimens combining dFdC plus radiation.


Cytosine methylation and suppression of O6-methylguanine-DNA methyltransferase expression in human rhabdomyosarcoma cell lines and xenografts.

Human tumor cell lines that do not express O6-methylguanine-DNA methyltransferase (MGMT) in detectable quantities (Mer-) are hypersensitive to the effects of O6-guanine-alkylating agents. Because the Mer- phenotype enhances tumor response to such agents, we investigated possible mechanisms involved in regulation of MGMT expression in a panel of Mer+ and Mer- pediatric rhabdomyosarcoma xenograft and cell lines. All Mer- cell and xenograft lines lacked not only MGMT activity but also the protein and mRNA as well, suggesting that its expression is transcriptionally regulated. Transfection of Mer+ and Mer- rhabdomyosarcoma cell lines with MGMT gene promoter-CAT constructs yielded similar levels of CAT expression, indicating that Mer- cells possessed the necessary factors to support transcription. Methylation in the 5'-untranslated region of the MGMT gene was assayed by Southern analysis using methylation-sensitive restriction enzymes. Digestion with HpaII and its methylation-insensitive isoschizomer, MspI, revealed little overall correlation between methylation and MGMT expression. However, methylation in a single SmaI site at position-69 was observed in all MGMT deficient lines but not in any MGMT expressing lines. These results suggest that methylation of specific cytosines in the MGMT promoter may play a role in suppressing its expression, as well as being a potentially useful marker for the Mer- phenotype.


5-hexyl-2'-deoxyuridine inhibition of nucleoside transport in L1210 cells.

Previous studies have shown that 5-hexyl-2'-deoxyuridine (HdUrd) blocked the cytotoxic effects of 5-fluorodeoxyuridine and deoxyadenosine in L1210 cells. HdUrd had no effect in preventing the inhibitory effects of 5-fluorouracil. These data suggested that HdUrd was an inhibitor of nucleoside transport in L1210 cells (Cory, J. G.; Halley, M. C.; Janey, A.; Lapis, K. Cancer Res. 50:4552-4556; 1990). Studies have now been carried out which show that HdUrd inhibits nucleoside transport as measured by [3H]uridine or [3H]formycin B transport into L1210 cells in culture. The IC50 for HdUrd inhibition of total [3H]uridine uptake was approximately 20 microM in wild-type L1210 cells. Since wild-type L1210 cells have three distinct nucleoside transporters, the effect of HdUrd on each transporter was examined using the non-metabolized nucleoside analog, formycin B. The nitrobenzylmercaptopurine riboside (NBMPR)-sensitive transporter, es, was most sensitive to HdUrd with an IC50 of 1.0 +/- 0.1 microM; the NBMPR-insensitive transporter, ei, was much less sensitive to HdUrd with an IC50 of 32 +/- 2 microM; the sodium ion-dependent transporter, cif, was the least sensitive transporter to HdUrd with an IC50 of 130 +/- 5 microM. These data support the concept that HdUrd, a relatively non-cytotoxic agent, could be useful in increasing the potency of antitumor inhibitors directed at the de novo pathways for nucleotide synthesis through the blockage of the salvage pathways for nucleosides.


EGF receptors in R3230AC rat mammary carcinomas: characteristics and regulation in vitro and in vivo.

Epidermal growth factor (EGF), at 10(-11) M and 10(-10) M, stimulated [methyl-3H]thymidine incorporation into DNA and cell growth of R3230AC mammary adenocarcinomas in primary cultures, whereas at higher concentrations (10(-9) M and 10(-8) M) EGF inhibited DNA synthesis and cell growth in vitro. To determine whether these responses were receptor-mediated, 125I-EGF binding to freshly dissociated cells and primary cultures of R3230AC cells was measured and found to be time- and temperature-dependent. Specificity of EGF binding was demonstrated by 50% displacement occurring at an EGF concentration of 0.46 nM. Using 125I-EGF concentrations from 0.05 nM to 10 nM, saturable binding sites were documented; Scatchard analysis of these data produced curvilinear plots, suggesting the presence of high affinity (0.44-0.93 nM) and low affinity (1.5-4.8 nM) sites. 125I-EGF was rapidly internalized by cultured R3230AC tumor cells. By 30 min, 73% (25 degrees C) and 77% (37 degrees C) of total 125I-EGF was internalized (resistance to acid/salt extraction), whereas at 4 degrees C, cells internalized only 20% of EGF over a 3 hr incubation period. Following incubation with 125I-EGF for 2 hr at 4 degrees C, 25 degrees C, or 37 degrees C, the majority of cell-associated radioactivity eluted with intact 125I-EGF. However, when the material that dissociated from R3230AC cells after the 2 hr incubation was analyzed, 38% (25 degrees C) and 46% (37 degrees C) of the radioactivity migrated as lower molecular weight products, indicating that 125I-EGF was partially degraded intracellularly by R3230AC cells in primary culture. Pre-incubation of cells in primary culture with EGF (1-100 nM) for 30 min at 37 degrees C, led to "down-regulation" of EGF receptors; 1 nM EGF reduced the specific binding of 125I-EGF by 54% with higher concentrations (10 nM and 100 nM) reducing it further. Scatchard analysis of down-regulated cells showed a reduced number of high affinity binding sites with no change in the Kd of binding. Sialoadenectomy of rats had no effect on R3230AC tumor growth or EGF receptor levels in the tumor, liver, or uterus. Experiments to determine whether perturbations of the insulin milieu or ovariectomy would alter EGF receptors were performed. 125I-EGF binding was significantly elevated in tumors from diabetic rats (152% increase vs controls) and binding was returned to control (77% of intact rats) levels after administration of insulin to diabetic rats.(ABSTRACT TRUNCATED AT 400 WORDS)


Bone marrow matrix promotes differentiation and prolongs the cell cycle of U-937 cells.

The extracellular matrix influences the growth and differentiation of a variety of cell types. In this study, the effects of bone marrow extracellular matrix on U-937 cells, a human histiocytic lymphoma cell line, were assessed. Sixty percent of U-937 cells adhered to extracellular matrix, whereas only 1% adhered to uncoated plastic. U-937 cells grown on extracellular matrix released significantly more lysozyme into the medium (8.3 +/- 0.3 micrograms/10(6) cells) compared to those grown on plastic (4.2 +/- 0.5 micrograms/10(6) cells). FMLP (f-met-leu-phe) receptor expression was also enhanced suggesting a more mature phenotype in cells grown on matrix (2980 cpm/10(6) cells vs 230 cpm/10(6) cells on plastic). Furthermore, bone marrow extracellular matrix inhibited proliferation of U-937 cells. After four days in culture, there was a 65% inhibition of cell growth in matrix-coated flasks compared to uncoated flasks. Since an arrest in G0/G1 usually precedes mammalian cell differentiation, DNA histograms were performed on U-937 cells grown on matrix to detect such an arrest. However, the cell cycle distribution of U-937 cells grown on extracellular matrix or uncoated plastic for various time periods was similar. In contrast, bromodeoxyuridine pulse labeling revealed approximately a 5 hr prolongation in cycle length in cells grown on extracellular matrix. We conclude that bone marrow extracellular matrix induced macrophage-like differentiation and inhibited proliferation of U-937 cells with a prolongation of the cell cycle that was not G0/G1 phase specific.


Contribution to the issue of essential drugs in Czechoslovakia.

To determine the ratio represented by essential drugs (EDs) in the total consumption of drugs in Czechoslovakia in 1989. Retrospective analysis of the assortment and consumption of EDs in 1989. Department of the Organization and Management of Pharmacy, Faculty of Pharmacy, Bratislava. Consumption of drugs and/or pharmacotherapeutic groups, expressed by the number of formulations, number of units, and in financial terms. EDs constitute approximately one-third of the total consumption of drugs in Czechoslovakia (both in terms of volume and finances); almost 60 percent of EDs have dosage forms and concentrations identical to those shown in the World Health Organization Model List of Essential Drugs (Sixth List). The results obtained indicate that there is need for a regular updating of the drug policy within the public health branch of the government to more effectively regulate the production and import of drugs.


Medication assistance: the development of drug surveillance and drug information in The Netherlands.

To describe the development of drug surveillance and drug information in The Netherlands. Historically, the professions of medicine and pharmacy have existed separately with little contact between them. Since the 1960s, this situation has changed in The Netherlands. Both professions are cooperating to an ever-increasing degree, primarily in the areas of computerized drug surveillance and individualized patient drug information, resulting in greater patient benefit. Exchange of knowledge between physicians and pharmacists, greater cooperation among professionals, use of computerized patient medical records, and involvement of the patient in his own healthcare will have a positive influence on the development of drug assistance in the future.


Possible correlation between glycemia and blood pressure in black, diabetic, hypertensive patients.

To determine if there is any association between glycemia and blood pressure in black patients with hypertension and diabetes mellitus whose antihypertensive medications had been unchanged for six months. Retrospective, from March 1990 through February 1991. Internal medicine ambulatory clinic at Detroit Receiving Hospital/University Health Center. Patients seen during this period with hypertension and type II diabetes. Of the 639 possible subjects, 124 met the following criteria: (1) no change in antihypertensive medications for six months, (2) absence of secondary hypertension, and (3) weight change (if any) was less than five percent. Changes in antihypertensive medication(s) excluded 388 patients, secondary hypertension excluded 3, weight changes of more than five percent excluded 94, and lack of matching postprandial capillary blood glucose (PCBG) values excluded 30. The mean age of the subjects was 66.8 years, mean diabetes duration was 12.0 years, mean PCBG was 10.7 mmol, mean systolic blood pressure (SBP) was 1543 mm Hg, mean diastolic blood pressure (DBP) was 90.1 mm Hg. There were 28 men in the study and 96 women; 90 were obese (body mass index greater than 25 kg/m2) and 34 were nonobese. The diabetes was managed with insulin in 67 patients, with sulfonylureas in 50, and with diet in 7. None SBP and DBP versus PCBG at matching time both at baseline and at six months. There was a positive association between blood pressure measurements and glycemia. Overall change in SBP was strongly correlated with PCBG changes (r = 0.745, p less than 0.0001). Improved glycemia correlated with improved SBP control (r = 0.330, p less than 0.0024). Deterioration of glycemia correlated with a worsening of SBP control (r = 0.445, p less than 0.0053). The method of blood glucose control had no statistically significant effect (ANOVA) on these results. Glycemia is positively associated with blood pressure.


Acceptance of a pharmacy-based, physician-edited hospital pharmacy and therapeutics committee newsletter.

To assess the level of physician acceptance and perceived usefulness of a pharmacy-prepared, physician-edited pharmacy and therapeutics (P&T) committee newsletter. Two separate surveys conducted after 7 and 24 months of publication, respectively. 500-bed, university-affiliated, tertiary-care hospital. The initial survey was mailed to physicians after 7 months of publication and they were requested to rate various aspects of the newsletter, including timeliness of articles, usefulness of articles, quality of writing and design, and overall value of the publication on a scale of 1-4: (1 = excellent, 2 = good, 3 = fair, 4 = poor). Physicians were also asked to rank different categories of articles (articles on new drugs, drug-class reviews, topical reviews, formulary news, and articles providing P&T committee information) and were encouraged to provide comments. A separate follow-up survey conducted at 24 months asked physicians to indicate whether they (1) regularly received the newsletter, (2) regularly read the newsletter, (3) found the information in the newsletter to be useful, and (4) desired to continue receiving the newsletter. Initial survey results yielded mean newsletter quality scores ranging from 1.54 to 1.66. Respondents preferred, in descending order, articles on new drugs, drug-class reviews, topical reviews, formulary news, and P&T committee information. The 24-month survey revealed that 96 percent of the physicians regularly receiving and reading the newsletter found the information useful and 97 percent felt that the newsletter should continue to be published. Favorable comments were also received from several prominent physicians. The results indicate strong physician acceptance of a pharmacy-prepared, physician-edited newsletter and provide information about the types of articles preferred by physicians in a university hospital setting.


Parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS: experience with thirteen patients.

Cryptococcus neoformans infections of the central nervous system affect up to ten percent of AIDS patients. Standard therapy with amphotericin B with or without 5-flucytosine has a high rate of failure, relapse, and toxicity. Fluconazole is a new triazole antifungal agent available in both oral and intravenous forms that has shown efficacy in the primary and maintenance treatment of cryptococcal meningitis in AIDS patients. In this open, noncomparative trial, we evaluated the safety and efficacy of intravenous fluconazole followed by oral fluconazole in the treatment of acute cryptococcal meningitis in AIDS patients. Thirteen AIDS patients with acute cryptococcal meningitis, or relapse after successful primary therapy, received 400 mg of intravenous fluconazole daily for 12-16 days followed by oral fluconazole 400 mg/d for the duration of primary therapy. If cerebrospinal fluid (CSF) cultures converted to negative within 32 weeks of treatment, the fluconazole dose was decreased to 200 mg/d as maintenance therapy. Fluconazole therapy was successful in six patients (46 percent) and unsuccessful in seven (54 percent). Of the seven patients considered unsuccessful, one demonstrated clinical improvement but remained CSF-culture positive, five were clinical failure and were switched to amphotericin B therapy, and one died after two weeks secondary to cryptococcal meningitis. No patient experienced any adverse reactions necessitating discontinuation of therapy. In this small group of patients, moderate doses of parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS patients demonstrated failure rates similar to those reported in other studies with fluconazole and with amphotericin B. As there was no difference in initial Karnofsky scores or the severity of disease in treatment successes versus failures, it is difficult to determine who might respond to fluconazole as initial therapy or who should be treated initially with another agent. Further studies and clinical experience are needed.


Development of a questionnaire for detecting potential adverse drug reactions.

To develop a comprehensive list of symptoms categorized by body system as part of a questionnaire for detecting potential adverse drug reactions. A preliminary list of symptoms in lay terminology was extracted from the "Side Effects" section of all drug monographs contained in the United States Pharmacopeia Dispensing Information (USP DI) computerized database (Volume II, Advice for the Patient) using natural language processing software. The list was sorted alphabetically and duplicate terms were eliminated. Symptoms were then categorized by body system or anatomic region. A preferred term for each symptom was selected when multiple synonyms and related words were listed. Finally, all of the symptom terms were incorporated into a thesaurus from which the questionnaire was derived. The questionnaire will be used as part of a computer-assisted interview, developed to solicit information from patients regarding their medication regimens and to systematically query them regarding the presence of salient symptoms or complaints. The computer system will eventually interface with the USP DI database to identify drugs from a patient's regimen that may be associated with adverse symptoms. The symptom thesaurus will provide the link to the USP DI database. Preliminary experience with the questionnaire in a limited number of patients has been encouraging. The questionnaire can assist clinicians in identifying drug-related symptoms including unreported adverse clinical effects of newly marketed or investigational therapeutic agents. When the questionnaire is computerized and linked to a comprehensive database, it can be more widely used to alert healthcare providers of potential adverse drug reactions that may otherwise go undetected.


Mercaptopurine-induced fever in a patient with Crohn's disease.

To report a case of mercaptopurine-induced fever. A patient with Crohn's disease was treated with mercaptopurine (6-MP) for an exacerbation of his illness. The patient developed fever and chills. After thorough diagnostic examinations and failure to respond to antimicrobial therapy, symptoms were attributed to an allergic-type reaction to 6-MP. The patient defervesced after 6-MP withdrawal. Fever and chills, along with arthralgias, recurred upon rechallenge with a single dose of 6-MP. Adverse effects attributable to 6-MP therapy in inflammatory bowel disease were reviewed in the literature. Drug-induced fever has been previously reported; however, it is an uncommon adverse effect and is difficult to diagnose. It is also difficult to predict which patients will have the reaction. It is a diagnosis of exclusion requiring a thorough investigation. Drug-induced fever should be considered when confronted with fever and chills in patients with inflammatory bowel disease being treated with 6-MP. This case report shows the difficulty in differentiating between an infectious process and an adverse reaction to a medication.


Relationships among prescription payment methods and interactions between community pharmacists and prescribers.

This research was performed to examine community pharmacists' interactions with prescribers and to determine if these interactions are related to payment method. Randomly selected pharmacists (47 in chain pharmacies and 26 in independent pharmacies) collected data concerning prescriber interactions for a 40-hour period. These interactions were analyzed in terms of payment methods, prescriber acceptance, and types of information discussed. Information concerning 730 interactions by 72 pharmacists was obtained. Payment methods were related to the frequency of interactions per pharmacist (p less than 0.01). There were higher percentages of interactions for self-pay (median 2.2 percent) and Medicaid (median 1.8 percent) prescriptions than for third-party fee-for-service (mode 0 percent) or capitation prescriptions (mode 0 percent). Type of information discussed was related to payment method. The vast majority of information provided by pharmacists (91 percent) was accepted by prescribers. The rate of acceptance was 97 percent for prescriber-initiated interactions versus 88 percent for pharmacist- or patient-initiated interactions (p less than 0.01). Relationships between payment method and interactions were identified. These findings may be attributable to prescribing policies and reimbursement policies. Prescribing policies that restrict prescribers to a formulary may help make them become more adept at using those products; thus, they will make fewer prescribing errors. Reimbursement policies that require patients to consistently use a specific pharmacy (i.e., capitation) may help pharmacists become more familiar with the patient's prescription history. Therefore, interactions with prescribers are needed less frequently for these patients' prescriptions.


Cefaclor-associated serum sickness-like disease: eight cases and review of the literature.

To describe the clinical features of serum sickness-like diseases (SSLD) in cefaclor-treated patients. Analysis of a case series spontaneously reported to Lyons Pharmacovigilance Center. General and hospital practitioners and the French Network of Regional Pharmacovigilance Centers (FNRPC). All reported cases with a possible causative relationship between cefaclor treatment and SSLD. Eight cases of SSLD following cefaclor treatment are described. The clinical features included cutaneous reactions, arthralgias, and moderate hyperthermia. In 50 percent of the patients, hospitalization was required because of incapacitating symptoms. The outcome was benign in all cases following discontinuation of the offending drug. All eight cases were reported in children under five years of age. Among 137 cefaclor-associated drug reactions collected by FNRPC, 27 cases of SSLD have been reported; 23 of these patients were younger than five years of age. A literature survey confirmed the higher reporting of SSLD in children with cefaclor compared with other antibiotics and suggested an incidence of 0.024-0.2 percent of SSLD per drug course of cefaclor. The case reports and epidemiologic studies confirmed the presumed role of age (patients under five years of age) in cefaclor-induced SSLD and the benign outcome despite severe clinical presentations in some reports.


Implication of dispensing cups in dosing errors and pediatric poisonings: a report from the American Association of Poison Control Centers.

To characterize reports to poison centers involving liquid medication errors associated with the use of dispensing cups. Case series reported by 16 US poison centers over an eight-day period. Calls to poison control centers, predominantly but not exclusively from homes. Children and adults. Of 34 reported cases, most (79 percent) involved a two- to threefold dosing error, and most (94 percent) involved an error in a single dose of medication. Cough and cold preparations were implicated in 65 percent; acetaminophen elixirs in 18 percent. Three major causes of dosing errors were identified, including teaspoon/tablespoon confusion, assumption that the dispensing cup was the unit of measure, and assumption that the full dispensing cup was the actual dose. Dispensing cup markings should use a single unit of measure, and a uniform labeling system should be implemented. Teaspoon/tablespoon abbreviations should be avoided, and dispensing cup lettering should be more legible. Consumer education is essential to correct the misimpression that the full cup is always the recommended dose.


Evaluation of medication knowledge in elderly patients.

To identify problems with medication knowledge, self-estimated compliance, and recall of medication education in a group of elderly patients. Survey. Medicine and geriatric clinics at a county hospital. Patients greater than or equal to 60 years old and taking at least one prescription medication. Medication knowledge, self-estimated compliance, and recall of medication education. The percent of geriatric patients correctly stating 76-100 percent of their medication doses, uses, and frequencies was 30, 64, and 66 percent, respectively. Fifteen patients (34 percent) stated they never missed a medication dose and 27 (61 percent) remembered to take their medications by memory alone. Sixteen and 86 percent, respectively, of the patients from the medicine and geriatric clinics could not recall receiving verbal or written educational material. Only 27 percent of patients recalled having been told about possible adverse reactions. The most frequently cited providers of medication information were physicians. Specially designed multidisciplinary medication education programs with repeated written and verbal reinforcement for elderly patients may improve patients' knowledge about their medications, recognition and management of adverse reactions, and compliance.


Possible intraoperative anesthetic-sparing effect of parenteral ketorolac.

Because the analgesic effects of ketorolac are equivalent to those of narcotic analgesics, we investigated the possibility that this non-steroidal antiinflammatory drug might also exhibit anesthetic-sparing properties similar to those described for narcotic agents. A nonrandomized, double-blind convenience sample. The treatment group received a preoperative dose of ketorolac 60 mg im 45 minutes prior to the induction of anesthesia. All other preoperative medications were identical. Brooke Army Medical Center, a primary care setting. Six women requiring vaginal hysterectomies from American Society of Anesthesiologists class I/II, all of similar age, weight, and body surface area. End-tidal concentrations of the anesthetic gas were measured at five-minute intervals using a gas analyzer. A mean percent end-tidal concentration versus time curve was generated for each group. The area under the concentration curves for the anesthetic gas in the ketorolac and control group were 15.9 +/- 5.1 and 52.3 +/- 13.4, respectively (p = 0.006). Ketorolac exhibits an anesthetic-sparing quality similar to that observed with narcotic analgesics.


Nightmare cessation following alteration of ophthalmic administration of a cholinergic and a beta-blocking agent.

To document the termination of nightmares brought about by an alteration in the ophthalmic administration of beta-blocking and cholinergic agents. A 75-year-old man residing in a long-term care facility experienced nightly nightmares of approximately one-year duration. Other potential causes for the nightmares were eliminated. The administration of the ophthalmic agents was evaluated and the resident was then instructed to alter administration to include closure of his eyes for one or two minutes after administration. Following the alteration in administration the nightmares were not present and have not reappeared in the ensuing year. Ophthalmic application of beta-blocking and cholinergic agents is used for the treatment of glaucoma and has been reported to cause a wide variety of central nervous system effects. Researchers have documented reduced systemic absorption and enhanced ocular retention time with specific modifications in the administration of the ophthalmic products. Based on this research the suggestion has been made that systemic adverse effects may be reduced by altering administration through use of lid closure and lacrimal occlusion. This case validates this hypothesis and provides strong evidence for the need to counsel all patients receiving ophthalmic agents on proper administration, including techniques to reduce absorption in order to avoid undesirable systemic effects.


Hypersensitivity immune reaction as a mechanism for dilevalol-associated hepatitis.

To assess lymphocyte reactivity to dilevalol and to serum containing putative ex vivo dilevalol antigens or metabolites in a case of dilevalol-induced liver injury. A 58-year-old woman with a clinical diagnosis of dilevalol-induced liver injury. Peripheral blood mononuclear cells collected from the patient were cultured in the presence of a solution of dilevalol and also with sera collected from a volunteer before and after dilevalol intake. A similar protocol was performed with lymphocytes from a healthy subject. No lymphocyte proliferation was observed either in the patient or in the healthy volunteer in the presence of dilevalol solutions. A significant proliferative response to serum collected after dilevalol intake was observed in the case of the patient compared with the proliferative response to the serum collected before the drug intake. No reactivity was found when lymphocytes from the healthy subject were tested under similar conditions. The methodology used allowed the detection of lymphocyte sensitization to sera containing ex vivo-prepared dilevalol antigens, suggesting the involvement of an immunologic mechanism in dilevalol-induced liver injury.


Weight gain associated with cinnarizine.

To report four cases of cinnarizine-induced weight gain. Case reports from a local obesity center and review articles. Data were abstracted from spontaneous comments made by patients to one of the authors, who was a doctor at the clinic, and reviewed by the remaining authors. We reviewed the cases of four women, aged 50-57 years without endocrine or metabolic pathologies, that showed weight gain associated with the intake of cinnarizine for one to two years. No other drugs usually were administered during the period in which the women gained weight, although in two cases cinnarizine was associated with dihydroergocristine in the same medicine (Clinadil). The mean weight increase was 6.25 kg (range 4-10). The increases do not appear to be related to whether the patients' initial weight was ideal or excessive. The weight gain was always associated with increased appetite and food intake. One patient discontinued cinnarizine treatment and her weight returned to its previous level. Cinnarizine is a piperazine derivative used in the treatment of vertigo and in the prophylaxis of migraine. In contrast to related drugs, data about cinnarizine are scarce because randomized trials of cinnarizine have been inconclusive. Our observations indicate that cinnarizine may cause weight gain, as observed with other drugs in the same class.


Ciprofloxacin-induced psychosis.

To report a case of ciprofloxacin-induced psychosis and to discuss occurrence rates, risk factors, possible etiologies, preventive measures, and treatment courses for this adverse reaction. Case reports and review articles identified by MEDLINE. Data from pertinent published sources were reviewed and abstracted. A 49-year-old man developed symptoms of severe psychosis concomitant with ciprofloxacin (250 mg bid) treatment. Central nervous system effects secondary to ciprofloxacin treatment are uncommon and usually consist only of minor dizziness or mild headache, although rare occurrences of seizures and hallucinations have been reported. The mechanism by which ciprofloxacin causes these adverse effects is not fully understood. It has been suggested that quinolones may produce an epileptogenic effect by inhibiting the binding of gamma-aminobutyric acid to its receptor sites in the brain. There is yet no explanation for the occurrence of hallucinations or psychosis. Caution should be exercised when using ciprofloxacin in the treatment of patients with personality abnormalities or symptoms of psychosis.


Pentostatin: an adenosine deaminase inhibitor for the treatment of hairy cell leukemia.

To review the pharmacology, pharmacokinetics, adverse effects, and various dosage regimens of pentostatin, and to evaluate the role of pentostatin in the treatment of hairy cell leukemia (HCL). Articles were identified via an English-language literature search of MEDLINE (1966-91) and an extensive search of bibliographies from identified articles. Human clinical trials and case reports were selected for evaluation. The literature was assessed for quality, methodology, and outcome information. At dosages of 4 mg/m2 administered every other week for 6-9 months, pentostatin has been shown to successfully induce a complete response in 58-90 percent of patients and to produce a partial response in up to 30 percent of patients with HCL. The median time to achieve a response is 4.7 months. Long-term remissions of at least 14 months' duration have occurred in some patients. Compared with interferon alfa alone, total response rates are not significantly different when pentostatin and interferon alfa are used in combination. When dosed appropriately, pentostatin is generally well tolerated. Common adverse effects include nausea, vomiting, myelosuppression, fever, and infection. Pentostatin is a purine analog that inhibits adenosine deaminase, a key enzyme necessary for purine salvage. Pentostatin has received labeling approval for the treatment of HCL refractory to a minimum of three to six months of treatment with interferon alfa. Based on current data, pentostatin will be a useful addition to the therapeutic agents presently available to patients with HCL. Ongoing trials are evaluating the effectiveness of pentostatin as first-line therapy for patients with HCL.


Psychotropic drug-related rhabdomyolysis.

The objective of this review is to discuss the pathophysiology and potential etiologies of rhabdomyolysis in psychiatric patients, with an emphasis on psychotropic drug-induced rhabdomyolysis. References were obtained through an on-line search of MEDLINE, using English-language and human literature only. Because the topic is a potential drug-induced adverse effect, no controlled studies are available. Most of the literature are case reports and series of case reports. The quality of case reports was assessed using the Food and Drug Administration guidelines for assessing the causality of a potential adverse drug reaction. The results of this review are based on qualitative data and indicate that rhabdomyolysis in psychiatric patients can be from multiple etiologies, including agitation, dehydration, and intramuscular injections, as well as an adverse effect of psychotropic medications. Although the deficiencies of this type of data are recognized, it is the only type of data often available to assess the etiology and causality of an uncommon adverse event. Rhabdomyolysis in psychiatric patients can be caused by many factors, both drug- and non-drug-related. Rhabdomyolysis is more likely to occur when patients are faced with a combination of risk factors. When combinations of factors are present (e.g., aggression and restraints, intramuscular injections, and extrapyramidal effects), or when muscle trauma from an individual factor is sufficiently traumatic, muscle necrosis may occur to the point that rhabdomyolysis ensues.


Selective decontamination of the digestive tract in intensive care patients: review and commentary.

To evaluate the benefits, risks, and costs of antimicrobial regimens used for selective decontamination of the digestive tract (SDD) in intensive care unit (ICU) patients. Information was obtained from clinical trials, review articles, abstracts, and textbooks. Key indexing terms included antibiotics, selective decontamination, and infections. Research articles describing controlled clinical trials of SDD in medical or surgical ICU patients were reviewed. Trials that investigated transplant, cirrhotic, leukemic, or oncology patient populations were excluded. The details of studies that evaluated nosocomial infection or nosocomial pneumonia rates were extracted. These included study design, demographics, SDD regimens, severity of illness scores, and colonization, infection, and mortality rates. The use of SDD in mechanically ventilated surgical or trauma ICU patients reduces the incidence of colonization, nosocomial pneumonia, and overall infection rates, but does not change the overall mortality rate. Administration of antibiotic and antifungal agents in a nasogastric suspension is required for SDD. The addition of systemic prophylactic antibiotics or oropharyngeal paste was not required to decrease nosocomial infections. The most frequently studied SDD regimen (colistin/amphotericin B/tobramycin) is not feasible for use in the US because of exorbitant drug costs. Less expensive alternatives include norfloxacin/nystatin, or colistin/nystatin/gentamicin. Additional research is required before SDD regimens can be routinely recommended in surgical and trauma ICU patients. A multicenter study is warranted to determine the long-range benefits, potential for resistance, and cost-effectiveness of SDD.


Short- and long-term retention of a nursing home education program on metered-dose inhaler technique.

To evaluate an education program on metered-dose inhaler (MDI) technique designed for nurses and trained medication aides (TMAs). The education program included a handout, a lecture incorporating a videotape on correct inhaler and device technique, and hands-on experience with placebo inhalers. The participants' ability to verbalize and demonstrate correct MDI technique was assessed by the same two-person teams before, immediately after, and two months after the program. Five nursing homes. Fifty-six nurses and TMAs practicing in nursing homes. Learning and retention. The participants' mean (+/- SD) verbal and demonstration scores increased immediately after the program by 68 +/- 18 points for verbalization and 47 +/- 16 points for demonstration. The participants were always better at demonstrating than verbalizing MDI technique. The participants' baseline verbal and demonstration scores correlated with the amount learned. Learning was influenced by the individual nursing home (verbal and demonstration) and personal use (demonstration only), but not by academic degree, previous training, past instruction of a patient, or current care of a patient who was receiving inhaler therapy. After two months, the scores were lower than immediately after the program test by 0-92 points for verbalization and 10-80 points for demonstration; however, the mean scores were still significantly greater (p less than 0.05) than the baseline scores. Retention of knowledge on the correct technique was greater for the demonstration component. Retention was influenced only by the nursing home in which the participant worked, and not any of the other variables. Our structured education program significantly improved inhaler technique; however, to maintain retention of the material, the program should be frequently repeated.


Analysis of IgA antibody to Pseudomonas aeruginosa in sera and sputa of patients with chronic airway diseases.

The change of IgA system for Pseudomonas infection was examined by enzyme-linked immunosorbent assay of the system in sera and sputa of patients with chronic airway diseases. The anti-Pseudomonas total IgA antibody titers in both sera and sputa were not elevated in group I with no infection (mainly chronic bronchitis) and group II infected with bacteria other than Pseudomonas, but were elevated in group III colonized transiently with Pseudomonas [diffuse panbronchiolitis (DPB) and bronchiectasis] and group IV colonized persistently with Pseudomonas (mainly DPB). The elevation in the sera and sputa were mainly due to monomeric IgA and polymeric IgA (S-IgA), respectively, and values were significantly higher in group III than in group IV only in the sera. These results indicate that the IgA system is enhanced in advanced DPB and bronchiectasis complicated by Pseudomonas infection, and that the anti-Pseudomonas IgA antibody titer in serum is more useful than that in sputum for the diagnosis of respiratory Pseudomonas infection.


Localization of exercise-induced myocardial ischemia with ST depression.

This study was undertaken to determine whether the site of ST depression on 12-lead exercise electrocardiography can identify the ischemic site assessed by myocardial Tl-201 emission computed tomography in 409 patients with transient defects. ST depression in some leads was more frequent in those with inferior or lateral ischemia than in those with anterior ischemia. In 214 patients with ST depression and no ST elevation, however, the frequency of ST depression in each lead was similar between those with and without anterior ischemia. In 63 patients with ST depression, single vessel disease and no infarction, the frequency of ST depression in each lead was similar among those with anterior, inferior and lateral ischemia. Moreover, in patients with abnormal Q waves, the site of ST depression was not related to the location of ischemia. In conclusion, the site of exercise-induced ST depression could not be used to determine an ischemic region.


A description of a pharmacotherapy curriculum in a university-based family medicine program.

To describe the methods by which a family medicine residency program implements a pharmacotherapy curriculum. The goal of the curriculum is to teach family medicine residents the principles of rational drug therapy. A university-based family medicine residency program. TEACHING STRATEGIES: Specific learning objectives are discussed and the following teaching strategies are expanded upon: (1) monthly noon conferences; (2) a printed formulary and pharmacotherapy handbook; (3) a pharmacy and therapeutics committee; (4) policy statements for drug representatives and use of samples; (5) an on-site pharmacy; (6) quarterly newsletter; and (7) inpatient consultation coverage. PHARMACIST ROLE: The role and responsibilities of the pharmacy faculty and pharmacist(s) who implement this curriculum and the methods used to evaluate its effectiveness are also described. The availability and funding of the pharmacy faculty member can sometimes be arranged with local schools of pharmacy seeking clerkship sites. Interaction with pharmacy students also serves to enhance the educational experience of the family medicine residents. The family medicine program implements a comprehensive curriculum designed to teach family medicine residents the principles of rational drug therapy. The curriculum may be expanded upon as necessary, or, if the entire program is not feasible, certain elements may be extracted and applied in other institutions.


Ultrasonography in the diagnosis of aldosterone-producing adenoma: is it useful?

The usefulness of ultrasonography (US) in the diagnosis of aldosterone-producing adenoma(s) (APA) was compared with computed tomography (CT) and adrenal scintigraphy in 13 patients. The initial examination with US could demonstrate four of seven right APA. Repeat examinations later in two patients whose tumors were initially not detectable did reveal a tumor in one patient. On the other hand, two left APA were delineated on the initial trial. The other seven left APA, except two small APA in one patient, could be delineated during repeat US examinations performed on other days. With CT, all APA were detected during the first or second trial except for the smallest one. The rate of localization by adrenal scintigraphy with dexamethasone pretreatment was 11 of 13 patients. CT had the highest localization rate. However, US was shown to be useful in the localization diagnosis of APA on repeat examinations with a high delineation rate comparable to CT.


Diagnosis and management of endobronchial tuberculosis.

We examined the records of sixty-one patients (17 males and 44 females) with endobronchial tuberculosis (EBTB). Smear tests of acid-fast bacilli were positive in 42 cases and cultures of tubercle bacilli (TB) were positive in 57. The main findings of chest roentgenogram on admission were as follows: no abnormal findings in 8, atelectasis in 30, infiltration in 25, and cavitary lesions in 6. The localization and cross-sectional extension of lesions confirmed bronchoscopically were as follows: trachea in 15, with 3 circular lesions (CLs). Right (R-) main bronchus in 19 with 11 CLs, left (L-) main bronchus in 18 with 11 of CLs, R-truncus intermedius in 14 with 6 of CLs, R-upper lobar bronchus (UB) in 17 with 12 CLs, R-middle lobar bronchus in 14 with 11 of CLs, R-lower lobar bronchus (LB) in 6 with 2 CLs, L-UB in 10 with 7 CLs and L-LB in 3 with 2 CLs. All cases were treated by combination chemotherapy with isoniazid, rifampicin, streptomycin and/or ethambutol and the rate of negative conversion of TB was good, but most of circular lesions resulted in severe bronchial stenosis or complete obstruction during and after chemotherapy, and no improvement was seen in any of the atelectasis cases at the cessation of chemotherapy. We discuss the points of early diagnosis and management of EBTB.


Metoclopramide: an analysis of inappropriate long-term use in the elderly.

To present a case of possible metoclopramide-induced tardive dyskinesia and document the frequent use of metoclopramide for inappropriate lengths of treatment in elderly, ambulatory subjects. Descriptive study that identified long-term users of metoclopramide among a population of 4515 elderly subjects. Participants in an ambulatory health-screening program in Florida (Florida Geriatric Research Program). Individuals (2898 women and 1617 men) over the age of 65 years who volunteered for annual health screening. All medication histories for participants were reviewed to identify subjects who reported metoclopramide use on at least one visit to the program. Thirty-four participants (0.75 percent) reported the use of metoclopramide during at least one visit. Eleven subjects (32.4 percent) reported that they had used this drug for longer than one year. Nine of the 34 subjects (26.5 percent) also reported the use of metoclopramide at their next annual visit. Results from this study suggest that metoclopramide is frequently prescribed inappropriately to treat gastrointestinal disorders. Long-term use of this drug exposes patients to an unnecessary risk of adverse drug reactions.


Cell profile and elastase activity in diffuse panbronchiolitis investigated by bronchoalveolar and bronchial lavage.

To examine the mechanism of tissue damage which causes bronchiolectasis in diffuse panbronchiolitis (DPB), the cellular components, elastase and its main inhibitor, alpha 1-protease inhibitor (alpha 1-PI) were measured in bronchoalveolar and bronchial lavage fluid (BALF and BLF) from 14 DPB patients. A predominant increase in the neutrophil count was observed in DPB. Elastase activity in BALF and BLF was about 1,000-fold higher in the DPB group than in the control group. An inhibitor study and a positive correlation between elastase activity and the neutrophil count in both lavage fluids from the DPB group indicated that the activity was mainly that of neutrophil elastase. Western blot analysis of alpha 1-PI showed that most of the alpha 1-PI in the lavage fluids from DPB group was degraded. These results indicated that neutrophil infiltration increases the level of elastase in the DPB lesions; this increase seems to be closely related to tissue damage.


Hepatic and renal dysfunction following nafcillin administration.

To review four cases of combined hepatic and renal toxicity that may be associated with the administration of nafcillin in adults. This type of adverse event with the use of nafcillin has not been previously documented in the literature. References from pertinent articles are identified throughout the text. Nafcillin is a widely used penicillinase-resistant penicillin. In four patients receiving nafcillin doses greater than 9 g/24 hours, changes in renal and hepatic function markers were noted within 72 hours of the initiation of nafcillin therapy. Laboratory values returned toward baseline when nafcillin therapy was discontinued. Elevations in blood urea nitrogen, creatinine, total bilirubin, and lactate dehydrogenase have been previously described in the literature for penicillin-like agents other than nafcillin. The exact mechanism for such toxicities as well as patient risk factors have not been clearly established. Caution should be taken when initiating nafcillin therapy. Evaluation of renal and liver function tests prior to initiating nafcillin therapy and within the first 72 hours appears warranted. If hepatic and/or renal toxicity is observed, discontinuation of nafcillin should be considered.


The first report of a case with acute myocardial infarction showing familial deficiency of creatine kinase.

A 46-year-old male patient was diagnosed as suffering from acute myocardial infarction, but his serum creatine kinase (CK) level was extremely low and no CK isozymes were detected in the serum. The total CK activities in the skeletal muscle amounted to only 2% of that of the control. Electrophoresis of the CK isozymes in the skeletal muscle showed that CK-MM was absent but the CK-BB and abnormal isozyme bands were present. There was no evidence of myocardial ischemia, although the exercise treadmill test revealed ST segment depression in the chest leads. One of the patient's sisters had an extremely low serum CK level suggesting inheritance of this abnormality. This is the first report of a case showing familial deficiency of CK.


Bence-Jones myeloma with pleural effusion: response to alpha-interferon and combined chemotherapy.

A 73-year-old female patient with myelomatous pleural effusions is described. She was admitted to our hospital with lumbago and emaciation. Laboratory findings revealed cytopenia and hypogammaglobulinemia. Immunoelectrophoresis demonstrated Bence-Jones monoclonal protein in the serum, but not in the urine. Bence-Jones myeloma was diagnosed by the bone marrow aspiration. Chest X-ray film, however, showed bilateral pleural effusions. Fluid cytology revealed numerous immature plasma cells, indicating pleural involvement. Intrapleural administration of alpha-interferon combined with systemic chemotherapy (oral melphalan-prednisolone with alpha-interferon im.) was successful in maintaining the resolution of pleural effusions. Intrapleural alpha-interferon administration seems to be effective in the management of myelomatous pleural effusions.


Horseshoe kidney and membranous glomerulonephritis with cold activation of complement.

A 48-year-old woman was admitted to our hospital because of proteinuria associated with persistent hypocomplementemia. Intravenous pyelography indicated the presence of horseshoe kidney without other abnormalities. Hypocomplementemia was caused by cold activation of complement. There were some findings suggestive of chronic liver disease (positive HCV antibody, hypergammaglobulinemia, low cholinesterase, etc.). Percutaneous renal biopsy showed the features of multiple evolutional phases of membranous glomerulonephritis.


Meningioma developed 25 years after radiation therapy for Cushing's disease.

A 44-year-old woman who had been therapeutically irradiated with 45 Gy to the sellar lesion for Cushing's disease has been in remission for 25 years. A large but asymptomatic brain tumor was accidentally found in the right middle fossa by a routine follow-up computed tomography. Upon surgical removal of the tumor, the histology revealed a fibroblastic meningioma. Although the incidence of meningioma following irradiation to pituitary adenoma is rare, a follow-up computed tomography should be taken to any possible late onset, and curable complication.


Hereditary angioedema: a case with ascites yet no symptoms in the family.

An interesting case of hereditary angioedema in a 26-year-old female is reported, with a finding of transient effusion of fluid into the peritoneal cavity during the attacks. The patient suffered from recurrent abdominal pain for several years, but no family members had any similar symptoms. In spite of repeated hospital admissions and many examinations, accurate diagnosis was not made until the most recent admission. The recognition of hereditary angioedema as a cause of acute and/or recurrent abdominal pain may avoid useless invasive procedures and lead to adequate treatment in other similar cases.


Methyldopa-induced colitis in a patient with membranoproliferative glomerulonephritis.

A 76-year-old man with membranoproliferative glomerulonephritis complicated by methyldopa-induced colitis is reported. Eight months after administration of methyldopa, mucous bloody stool was noted. A barium enema examination showed disappearance of haustra and a spastic rectosigmoid with pseudo-polyposis. Biopsy specimens obtained from the sigmoid mucosa revealed interstitial edema and small inflammatory cells. After cessation of methyldopa treatment, the sigmoid findings, blood pressure, and proteinuria were improved, suggesting that methyldopa not only induced the acute colitis but also worsened the nephrotic syndrome in this patient.


Interstitial nephritis associated with glomerulonephritis in a patient with Hashimoto's disease and idiopathic portal hypertension.

A middle-aged women with hypothyroidism, idiopathic portal hypertension and nephrotic syndrome is presented. This unusual clinical appearance could not be explained as SLE by serological examinations. Pathohistological examinations showed "Banti's liver", Hashimoto's thyroiditis and diffuse proliferative glomerulonephritis with severe tubulo-interstitial nephritis. Immunohistochemical studies revealed IgA deposits in glomeruli. Electron microscopic study disclosed peculiar lucent areas of rarefaction with osmiophilic particles in tubular basement membranes. This tubulointerstitial nephritis was considered to be related to the immunological mechanism involving thyroid gland, liver and kidney disorders. This case thus had a clinically rare combination of these three.


A successful therapy with plasma exchange for interstitial pneumonia of progressive systemic sclerosis.

A 47-year-old woman who was diagnosed as progressive systemic sclerosis (PSS) had acute and severe interstitial pneumonia. Based on the results of her chest roentgenogram, computed tomography, transbronchial lung biopsy (TBLB) and bronchoalveolar lavage (BAL), her interstitial pneumonia was considered to be atypical of PSS. Although she was treated with corticosteroid, methylprednisolone pulse therapy and immunosuppressive drug, the effect of these drugs was insufficient as treatment for the interstitial pneumonia. Therefore, plasma exchange was attempted. After plasma exchange was carried out for three days, her symptoms improved as well as the laboratory data and chest roentgenogram without any severe side effects. We recommend plasma exchange for interstitial pneumonia of PSS as an effective treatment.


Primary malignant lymphoma of the trachea and subglottic region.

A 44-year-old female was admitted with the complaint of choking. On fiberbronchoscopic examination, multiple, polypoid lesions with a smooth surface were exhibited at the cervical trachea. Histological diagnosis was B-cell malignant lymphoma, diffuse, medium sized cell type (LSG classification). No other lesions were detected in the systemic evaluation. After combined chemotherapy and regional irradiation, the tumor disappeared. The clinical and pathological characteristics of this case are similar to those of malignant lymphoma of mucosa-associated lymphoid tissue (MALT).


Hemoglobin Andrew-Minneapolis (beta 144 (HCl) lysine----asparagine) in a Japanese family.

Hemoglobin Andrew-Minneapolis, an abnormal hemoglobin with an asparagine residue substituted for a lysine at position 144 of the beta-globulin chains, was identified in three members of two generations in a Japanese family. The carriers of hemoglobin Andrew-Minneapolis showed false high levels of hemoglobin A1c, as measured by the standard cation exchange high performance liquid chromatography, and a moderate tendency for erythrocytosis. This family is the first report of this abnormal hemoglobin in Japan.


Hypokalemic paralysis associated with distal renal tubular acidosis.

A 68-year-old man had hydronephrosis due to ureteral stones for two months earlier and then increasing muscle weakness developed. A 30-year-old woman had rapidly progressive quadriparesis. In both cases, severe hypokalemia with metabolic acidosis was observed and the diagnosis of distal renal tubular acidosis was made. The former was considered to be an idiopathic incomplete form and the latter was a secondary complete form associated with Sjögren syndrome. Hypokalemic paralysis may occur as a complication of distal renal tubular acidosis.


An autopsy case of intravascular lymphomatosis (neoplastic angioendotheliomatosis) accompanied by high fever, hypertension and without focal sign.

A 75-year-old woman suffered from intermittent high-grade fever and hypertension without any focal sign. Serum lactic dehydrogenase (LDH) was markedly elevated. The fever was resistant to antibiotics and temporarily sensitive to prednisolone. She had heart failure and died. Postmortem examination revealed intravascular proliferation of B lymphocytes, indicative of the diagnosis of intravascular lymphomatosis. The clinical diagnosis is usually very difficult because of the absence of pathognomonic clinical manifestations.


Ehlers-Danlos syndrome combined with von Recklinghausen neurofibromatosis.

We recently had the opportunity to study a 25-year-old male with both Ehlers-Danlos syndrome (EDS) and von Recklinghausen neurofibromatosis (VRNF). We describe the clinical manifestations of the case and discuss the probable pathomechanism of the combination of the two syndromes, with a review of the literature. As recent literature suggests that both syndromes are linked to chromosome 17, we conclude that their combination is not coincidental, but genetically linked.


Follicular bronchiolitis associated with rheumatoid arthritis.

Follicular bronchiolitis is a rare disorder, though it has been recognized as a pulmonary involvement of rheumatoid arthritis in recent years. A 57-year-old woman with rheumatoid arthritis was admitted to the hospital with persistent productive cough and breathlessness on exertion. An open lung biopsy was performed to establish a definite pathologic diagnosis of her disease, and she was diagnosed as having follicular bronchiolitis on the basis of the histopathological findings. It is essential to differentiate this disease from other bronchiolar or lymphoproliferative disorders of the lung.


Lupus nephritis associated with bacterial panperitonitis and lung alveolar hemorrhage.

A 36-year-old woman was admitted to the hospital with the diagnosis of nephrotic syndrome due to lupus nephritis. The patient had panperitonitis caused by Staphylococcus aureus as a complication, and an emergency laparotomy was performed. After the operation, the patient developed a massive lung alveolar hemorrhage. Methylprednisolone pulse therapy showed a marked effect on the lung hemorrhage. It is known that lung alveolar hemorrhages associated with systemic lupus erythematosus have a very high mortality; the present case is relatively rare because of the good response to steroid pulse therapy.


A 34-year-old man with Sweet's syndrome associated with subacute necrotizing lymphadenitis is reported. Histological examination of an erythematous, painful, cutaneous plaque revealed a dermal interstitial neutrophilic infiltrate. A biopsy specimen obtained from an inguinal lymph node showed granulomatous formation, consisting of histiocytes, with central necrosis in the paracortex and macrophages in the sinus. Although the causes of the two diseases remain obscure, this appears to be the first report of Sweet's syndrome associated with subacute necrotizing lymphadenitis.


The first report of diffuse panbronchiolitis in Korea: five case reports.

Diffuse panbronchiolitis (DPB), which is prevalent in Japan, is known to be rare outside Japan. Although a case of diffuse panbronchiolitis in a second generation Korean was reported in Japan in 1986, no case has been reported in Korea. Recently we found 5 cases of diffuse panbronchiolitis in Korea, two histologically proven and three clinically and radiologically suspected. All 5 cases had the typical respiratory symptoms and signs and a history of chronic sinusitis. In three clinically and radiologically suspected cases, high resolution computed tomography showed the typical findings of DPB and other diseases such as pulmonary emphysema, bronchial asthma, chronic bronchitis and bronchiectasis could be ruled out. More cases of DPB are expected to be found in Korea in the near future.


A new variant of alpha-1-antitrypsin deficiency (Siiyama) associated with pulmonary emphysema.

A 38-year-old male with pulmonary emphysema due to severely reduced serum alpha-1-antitrypsin (AAT) level (14.5 mg/dl) was found to have an inherited new AAT deficient variant Siiyama. Chest roentgenogram and CT scanning revealed advanced emphysema, and severe obstructive ventilatory impairment was observed. During the 4-year follow-up period, the annual rate of decline of FEV 1.0 showed approximately 10-fold greater than the normal decline in FEV 1.0 (-380 ml/yr). Treatment with tamoxifen in order to raise the serum AAT level only resulted in an insufficient increase. Augmentation therapy of human AAT should be considered in the future.


Acute renal failure following hypokalemic rhabdomyolysis due to chronic glycyrrhizic acid administration.

A 72-year-old man developed acute renal failure (ARF) following severe hypokalemic rhabdomyolysis. The hypokalemia was due to chronic glycyrrhizin (glycyrrhizic acid) administration. Although glycyrrhizin-induced hypokalemic rhabdomyolysis has been occasionally reported, the association of this type of rhabdomyolysis with ARF has not been described. In the present case, there was a sensitivity to glycyrrhizin the preceding renal insufficiency, and dehydration which was thought to have contributed to ARF. It should be recognized that elderly patients with such predisposing factors may be susceptible to a rapid deterioration of renal function after glycyrrhizin-induced hypokalemic rhabdomyolysis.


Pharmacological treatment strategies in age-related cataracts.

Cataract is the major cause of blindness worldwide and at present the only approved treatment in many countries including the UK and USA is surgical removal of the lens. In other countries various anti-cataract drugs are available without proof of their efficacy. Research is continuing into the possible benefits of several groups of drugs and some vitamins. The first to be studied were sorbitol-lowering agents (aldose reductase inhibitors) based on the sorbitol hypothesis for diabetic cataract. Sorbitol-lowering agents have distinct effects in vitro and many of them delay the development of cataract in galactose-fed rats. A few delay cataract in diabetic rats but none have been proved effective in clinical trials, although these continue. Aspirin, paracetamol (acetaminophen) and ibuprofen delay diabetic cataract in rats, and have been shown to delay other experimental cataracts. Case-control studies from 3 continents indicate that these drugs, or at least aspirin, protect against cataract. Results of studies on all 3 drugs indicate a benefit even at low doses. Population-based studies did not identify any protection against early lens opacities but tiny opacities that do not impair vision are not a problem. Bendazac protects lens proteins in vitro and delays cataractogenesis in x-irradiated rats. In humans, it reached the clinical trial stage but most trials have been small and with subjective criteria of opacification. One objectively monitored trial suffered from a high drop-out rate. Other preparations studied less extensively include vitamins, aminoguanidine to prevent protein cross-linking in diabetes and agents designed to boost glutathione levels. It is probable that some agents which may delay or prevent cataract will be proved effective soon, and in the end there may be different drugs to delay cataract in different high risk groups. This is what might be expected of a multifactorial disease, although compounds that intervene in the final common pathways to cataract could have a broad efficacy.


Nimodipine. A review of its pharmacological properties, and therapeutic efficacy in cerebral disorders.

Nimodipine is a dihydropyridine calcium antagonist which dilates cerebral blood vessels and increases cerebral blood flow in animals and humans. Preliminary findings reveal its potential benefit for the treatment of a wide range of cerebrovascular disorders, particularly for prophylaxis and treatment of delayed ischaemic neurological deficits resulting from cerebral vasospasm in patients with subarachnoid haemorrhage. Studies involving patients aged up to 79 years have confirmed these preliminary findings by showing that nimodipine reduces the incidence of severe ischaemic deficit after subarachnoid haemorrhage. Initial results from studies of patients with acute ischaemic stroke indicate that nimodipine, started within 72 hours of onset, improved recovery, particularly in patients over 65 years. However, other investigators have found no marked difference in 6-month mortality or morbidity rates of stroke patients aged up to 97 years. Findings from other studies suggest that nimodipine may improve symptoms of cognitive dysfunction in elderly patients. Nimodipine is well tolerated by both younger and older patients. The most frequently reported adverse event has been hypotension. Thus, nimodipine therapy offers important benefits as part of the approach to management of patients with subarachnoid haemorrhage and has potential in other cerebral disorders, including stroke and impaired cognitive function, although confirmation of initial results in patients with cerebral impairment are required.


The management of diabetic proteinuria. Which antihypertensive agent?

Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject.


Rapid induction of atherosclerosis in rabbits.

Japanese white rabbits fed a restricted amount (100 g/head/day) of an atherogenic diet (AD) containing 0.2% cholesterol and 6% peanut oil showed mild and persistent hypercholesterolemia (338 +/- 79 mg/dl). They developed atherosclerotic lesions 4 weeks after deendothelialization of aorta carried out at the 4th week of AD-feeding. This rabbit model of atherosclerosis has such advantages as being able to be produced in a short period and having similar biochemical and pathological characteristics with those in human atherosclerosis.


Bronchial-associated lymphoid tissue (BALT) response to airway challenge with cigarette smoke, bovine antigen and anti-pulmonary serum.

The bronchial-associated lymphoid tissue (BALT) is a lymphoepithelial organ, related to the immune defence of the lung and to alveolar clearance, which changes size in certain states of disease. Changes in the size of BALT were quantified and compared, and Spearman's test was used to test the relation with the bronchial epithelium. A total of 180 rats were used, divided into 6 groups of 30 as follows: 1) untreated controls; 2) exposed to cigarette smoke for two months; 3) treated with anti-pulmonary serum three doses daily over five days; 4) exposed to cigarette smoke and treated with anti-pulmonary serum; 5) sensitized with bovine albumin and exposed to an environment containing this antigen for two months; 6) exposed to cigarette smoke and bovine albumin. The lungs were processed for histological study, and were stained with the PAS-Alcian blue method. The main left bronchi BALT was studied, and the following were quantified: Lymphatic area (LA), as a percentage of the lung surface occupied by BALT; the flat epithelium (FEp), as the length of bronchial epithelium anatomically related to LA, whose cells tend to adopt a flat shape; the Contact epithelium (Cep), as the length of bronchial epithelium which is in direct contact with the LA. A percentage count of bronchial cells was made in the following classifications: globet cells; globet cells stained with the PAS-Alcian blue method; flat cells; lymphoepithelium cells; columnar cells; and bronchial epithelium cells excluding the above two cell types.(ABSTRACT TRUNCATED AT 250 WORDS)


Impotence in elderly men.

Impotence is a highly prevalent condition occurring in 10 million American men over the age of 18 years. Alterations in vascular supply, hormonal changes with age, neurological dysfunction and the use of a variety of medications may combine and contribute to impotence. Impotence should not be considered a normal part of the aging process. Careful attention to evaluation for the aetiology of impotence will lead to making appropriate therapeutic choices.


Presence of melanin in normal human Schwann cells.

The presence of melanin granules in Schwann cells of unmyelinated nerve fibres in the normal skin of a black woman is demonstrated by electron microscopy. Pathological conditions associated with the differentiation ability of Schwann cells for melanogenic are reviewed. This capacity may be due to the common origin of Schwann cells and melanocytes in the neural crest.


Studies on the interaction between titin and myosin.

This study examines the interaction of titin and myosin. In order to analyze the domains of myosin contributing to the binding for titin, we conducted a solid phase binding assay. Different portions of myosin (heavy chains, light chains and myosin fragments) were coated on the microtiter wells and reacted with biotinylated titin. Then the binding of biotinylated titin to these polypeptides was detected by using the avidinbiotin-peroxidase method. The results demonstrated that light meromyosin and subfragment 1 were the major domains of myosin interacting with titin. Titin fragments obtained by trypsin digestion were allowed to react with myosin in an affinity column, and the bound fragments were isolated by an acidic elution. Immunoblot analysis of myosin-bound titin fragments revealed that an A-band domain of titin was responsible for the binding of myosin. In addition, biotinylated titin labelled the outer A-bands and Z-bands in intact myofibrils, thus confirming the in situ binding of titin to myosin.


A scanning and transmission electron microscopic study of the membranes of chicken egg.

Questions regarding the structure of the inner and outer shell membranes of the chicken egg were addressed in this study by correlating observations from light microscopy and scanning and transmission electron microscopy. The egg membrane had a limiting membrane, which measured .9 to .15 microns in thickness and appeared to be a continuous and an impervious layer, but the shell membrane did not. Under the SEM, each membrane was seen to be made up of several fibre layers. In the tear preparations viewed under the SEM two layers were observed in the egg membranes and three to five layers in the shell membrane, with an apparent plane of cleavage between each layer. Each fibre was made up of a central core and an outer mantle layers. The central core was perforated by channels which measured .08 to 1.11 microns in diameter and ran longitudinally along the length of the fibre. Between the mantle layer and the fibre core was a gap or cleft measuring between .03 to .07 microns. The diameter of the fibres of the inner layer of the egg membrane ranged between .08 to .64 microns, whereas those of the outer layer of the same membrane ranged from .05 to 1.11 microns. Fibres in the shell membrane ranged from .11 to 4.14 microns diameter.


The pathophysiological role and therapeutic implications of platelet activating factor in diseases of aging.

Platelet activating factor (PAF) is a unique phosphoglyceride which possesses many potent biological activities relevant for the pathogenesis of diseases of the elderly. PAF is generated and released by numerous cell types and tissues and is rapidly metabolised through a well defined metabolic cycle. Its biological actions are mediated via direct and indirect stimulatory effects on target cells and tissues. The current knowledge of PAF and its role in cardiovascular disease, thromboembolism, cerebral ischaemia and neurodegenerative disorders are discussed in detail. It is likely, that in future, a better understanding of the pathophysiological and physiological roles of PAF will provide new strategies for the treatment of human diseases of aging.


The use of oral fluoroquinolones in nursing home patients.

The approach to management of patients with presumed infection in the nursing home is influenced by the limited availability of diagnostic tests and support staff. Although antibiotics are most often prescribed in the absence of laboratory data, many studies indicate that empirical therapy for nursing home infections is relatively successful. With the scrutiny on containment of healthcare costs, therapy of nursing home patients has been changing and will continue to shift toward treatment within nursing homes without transfer to a hospital. Better oral antimicrobial agents with a wide spectrum of activity, such as the fluoroquinolones, will play a major role in the treatment of many infections acquired in the nursing home. Because of the favourable characteristics of the fluoroquinolone agents, they should be useful for elderly patients who develop infections in nursing homes. They have excellent in vitro activity against Gram-negative bacteria which are often multidrug-resistant and are common in nursing home patients. Studies indicate that absorption of orally administered fluoroquinolones is very efficient in the elderly and these drugs are well tolerated. Numerous clinical trials have documented good efficacy of the fluoroquinolones in the treatment of elderly patients for the most common infections in the nursing home, including urinary tract infections, respiratory tract infections and skin infections.


In vitro analysis of the cellular resistance to chemotherapeutic BCNU.

Our assays in vitro show that BCNU inhibits cell proliferation in the C6 cell line experimental glioma and is dose-dependent, starting from 0.5 microgram/ml of the drug with just an hour of exposure. For every tested concentration of BCNU it is shown that, from the fifth day after exposure, cellular resistance appeared. This resistance is justified by the capacity of cell DNA reparation. A study of the clonogenic capacity of the C6 cells exposed to BCNU also shows the appearance of cellular resistance for doses of 0.5 microgram/ml and 1 microgram/ml. Furthermore, the exposure of C6 cell cultures to BCNU at these levels produces a cellular evolution towards more differentiated morphological patterns.


Hematoencephalic barrier. Ultrastructure and histophysiology of the endothelium capillary of the neuronal nuclei of the mesencephalon.

The ultrastructure of the dorsal periaqueductal nucleus capillaries of the mesencephalon in the cat was studied under the electron microscope in relation to the hematoencephalic barrier, and its four structural levels: 1. Endothelium; 2. Basal membrane; 3, Pericytes; and 4. Glial prolongations. An analysis was performed of what occurs in these four components (in a non-experimental histophysiological state, and without manipulation by markers) in the thinnest capillaries of the centre of the mesencephalic neuronal nucleus. Special attention was placed on the first diffusion barrier formed by the endothelium capillary as the intimate guardian of the Central Nervous System (C.N.S.) neurons. The C.N.S. capillaries are formed from the continuous endothelium, with no fenestrations, and hermetic joining complexes, without pinocytosis vesicles on both sides of the plasmatic membrane (adluminal and external), and surrounded by a continuous basal membrane. The non-fenestrated capillaries of the C.N.S. are less permeable than those with similar characteristics located in other areas. In the C.N.S. these capillaries form a selective physiological barrier which determines the size of the molecules that are permitted to cross the capillary wall. It is suggested that the electron-dense globules found in the endothelium cytoplasm may be molecules assimilated from the blood, which might represent the first level or step to the selective diffusion entrusted to the hematoencephalic barrier. It is also suggested that the elongated electron-dense particles found in the endothelium cytoplasm and basal membrane may be macromolecules which are normally retained for an active defensive function. They would represent the first and second level or steps of the retention performed by the hematoencephalic barrier which blocks their passage to the confined space of the perivascular capillary.


Ultrastructure of murine cardiac ganglia in experimental Chagas' disease.

Albino mice, infected with Trypanosoma cruzi (Tulahuen strain) were sacrificed on days 7, 9, 12, 14, 16, 18, 21, 32 and 39 following infection. Transmission electron microscopic examination of the cardiac ganglia revealed no ultrastructural change at day 7. At day 9 there was peri- and intraganglionic monocytic infiltration but parasites were absent. Between days 12 and 16 there was intense monocytic infiltration, with intra-ganglionic presence of parasites within fibroblasts, monocytes and macrophages. None were seen within capsular cells, endothelial cells, Schwann cells, satellite cells and ganglion cells. The Schwann cells and satellite cells, however, showed phagocytic activity. Satellite cells were also reactive with proliferative pseudopodia which encircled neuronal processes. By day 18, parasites were absent in the ganglia. But monocytes were still present up to day 39, some of them still engulfing satellite cell and neuronal processes. Satellite cells continued to be reactive and Schwann cells phagocytic. Ganglion cells remained normal throughout the experiment. The results suggest that infection of Schwann cells, satellite cells and ganglion cells may depend upon the tissue tropism of the strain of the parasite used and its concentration in the inoculum. The results are consistent with the view that any parasympathetic dysfunction in experimental Chaga's disease in the mouse may be of a transient nature.


Adverse reactions as a cause of hospital admission in the aged.

Truly elderly people comprise an increasingly large fraction of the population and consume a disproportionate amount of drugs. Over the last 25 years a number of different studies have illustrated that advancing age is associated with adverse drug reactions (ADRs). Advancing age is also associated with polypharmacy and multiple pathology, and this complex inter-relationship makes it difficult to conclude that age itself is a causative factor for ADRs. ADRs resulting in hospital admission have been the subject of study for many years, but it has not been consistently demonstrated that advancing age is a predisposing factor. Early studies used the method of intensive inpatient monitoring and identified digoxin, diuretics, aspirin, psychotropics and cytotoxics as drugs of concern. Smaller more recent studies have used more sophisticated statistical techniques to identify predisposing factors. Nonsteroidal anti-inflammatory drugs have been added to the list of drugs that may cause ADR-related hospital admission. Polypharmacy, and altered pharmacokinetics and pharmacodynamics are possible causative factors; however, variable compliance and multiple pathology may cause difficulties with attributing causality. Some basic guidelines for sensible prescribing would almost certainly result in fewer ADRs in the elderly, including those ADRs severe enough to result in hospital admission.


Structural and ultrastructural modifications of adenohypophyseal gonadotropic cells in goat (Capra hircus) in anoestrus, gestation and milk production.

The structural and ultrastructural modifications of the gonadotropic cells of goats were studied with an immunohistochemical method (peroxidase-antiperoxidase), in anoestrus, gestation and milk production. The cell type which predominates in anoestrus corresponds in its morphological characteristics to the classic FSH cells, and has two populations of homogeneous and electrodense secretory granules (141-244 nm and 244-400 nm in diameter), rough endoplasmic reticulum of flat cisternae and many large-sized lysosomes. During gestation secretory granules show a characteristic reduction in size and are less abundant; lysosomes are also more scarce and the endoplasmic reticulum shows a high development; dilated and intercommunicated cisternae show a slight electrodense content, characteristic of typical LH cells. During milk production the cells show an increase in the number of secretory granules which are still small, and an increase in the number of lysosomes which appear as in anoestrus.


Distribution of neuropeptide Y-like immunoreactivity in the brain of Salmo salar and Gambusia affinis.

Through the immunohistochemical PAP technique, the distribution of immune positive neurons and fibres for an antibody anti-NPY in the encephalon of salmon fixed in Bouin have been located and studied. NPY-positive neurons are found forming three important nuclei: in the ventrolateral telencephalon; in the tegmentum mesencephali; and in the locus coeruleus. Neurons in the optic tectum, in the thalamic region and a few in the preoptic recess have also been located. The fibres were found throughout the brain, with the exception of the cerebellum, presenting a greater density in three regions: in the dorsal telencephalon; in the mesencephalon; and in the visceral lobes in the rhombencephalon. With the aim of proving if this distribution is found in other groups of teleosts, we processed, with the same technique, the advanced teleost Gambusia affinis, in order to compare it with the primitive teleost Salmo salar. The results show that in both fish this neuropeptide has the same pattern of distribution. The results also suggest that in fish this neuropeptide can be involved in several functions of the central nervous system, as has been demonstrated for mammals. The innervation of the visceral lobes and also the presence of NPY-fibres in the posterior hypothalamus are anatomical supports of the studies which suggest that NPY is related to the control of the food intake.


Scanning electron microscopic and light microscopic observations on morphological changes of freeze-dried bone implantation in rats: comparison with fresh autogenous bone transplantation.

Bone remodelling after the implantation of freeze-dried autogenous bone in rat parietal bone was compared with fresh autogenous bone transplantation, using a scanning electron and light microscope revealed the time intervals after transplantation/implantation. The light microscope revealed the time delay of the bone remodelling in the implantation, compared with the transplantations. The scanning electron microscope showed that the differences between the two groups were in the states of bone union and bone resorption. In the fresh bone group, the newly-formed bone filled the spaces between host and the transplanted bones at 2 to 3 weeks after the transplantation: the newly-formed bone fused and melted into the transplanted bone. New bone formation was more dominant on the bone surface in the dura mater side than in the skin side. The union was almost completed at 5 weeks. In freeze-dried bone implantation, the bone union in the contact space was very poor and the implanted bone was mainly covered by the new bone, which developed from the host bone surface in the dura mater side at 2 to 3 weeks after the implantation. What is noteworthy is that bone resorbed areas showing numerous Howship's lacunae were mainly observed on the host bone surface in the vicinity of newly-formed bone. However in freeze-dried bone implantation, the bone resorption was greater on the host and implanted bone surface than that of fresh bone transplantation: the resorption of host bone was considerably larger at certain periods after freeze-dried bone implantation. The present results show that the healing process of freeze-dried bone implantation, even though autogenous bone was used, differed from that of fresh autogenous bone transplantation, and the differences are concerned not only with time sequences but also with qualitative changes. This suggests that the host would have some different responses to the freeze-dried autogenous bone from fresh materials.