Ovine pulmonary surfactant induces killing of Pasteurella haemolytica, Escherichia coli, and Klebsiella pneumoniae by normal serum.

Pulmonary surfactant has been shown to play an increasingly important role in bacterial clearance at the alveolar surface in the lung. This study describes a bactericidal mechanism in which ovine pulmonary surfactant induces killing of Pasteurella haemolytica by normal serum. To demonstrate killing, six bacterial species were incubated first with pulmonary surfactant for 60 min at 37 degrees C and then with serum for an additional 60 min at 37 degrees C. P. haemolytica type A1 strains 82-25 and L101, a P. haemolytica type 2 strain, Escherichia coli, and Klebsiella pneumoniae were susceptible and Pasteurella multocida, Serratia marcescens, and Pseudomonas aeruginosa were not susceptible to killing by ovine pulmonary surfactant and normal serum. No bacteria incubated with bovine pulmonary surfactant were killed by normal serum. Although the species origin of pulmonary surfactant was selective, the species origin of serum was not. P. haemolytica incubated with ovine pulmonary surfactant was killed by fetal calf serum, gnotobiotic calf serum, pooled normal sheep serum, pooled normal rabbit serum, and pooled guinea pig serum. Ultrastructurally, killed P. haemolytica suspensions contained dead cells and cells distorted with vacuoles between the cytoplasmic membrane and the cytoplasm. The mechanism of killing did not correlate with concentrations of complement or lysozyme or titers of residual antibody in either the pulmonary surfactant or the serum, and killing was reduced by preincubation of surfactant with P. haemolytica lipopolysaccharide. Preliminary characterization of both surfactant and serum implicate a low-molecular-weight proteinaceous component in the surfactant and serum albumin in the serum. This mechanism may help clear certain gram-negative bacteria from the lungs of sheep as a part of the pulmonary innate defense system.


Dual roles for class II major histocompatibility complex molecules in staphylococcal enterotoxin-induced cytokine production and in vivo toxicity.

The staphylococcal enterotoxins (SE) specifically bind to class II major histocompatibility complex (MHC) proteins, resulting in activation of monocytes and T cells. The SE cause weight loss in mice, which is dependent on T-cell stimulation and tumor necrosis factor alpha (TNF-alpha) production. Here we use a mutant of staphylococcal enterotoxin A that binds class II MHC molecules and activates monocytes but not T cells to evaluate the relative contributions of monocyte- and T-cell-stimulatory activities to in vivo toxicity. The mutant toxin did not cause weight loss in B10. BR mice but did stimulate monocyte TNF-alpha production in vitro, as did the wild-type toxin. Addition of a supernatant from toxin-activated T cells enhanced monocyte-stimulatory activity of both mutant and wild-type toxins fivefold. The effect of the supernatant could be mimicked by recombinant gamma interferon (IFN-gamma) and was inhibited by antibody to IFN-gamma. These results suggest that toxin-induced monocyte TNF-alpha production is upregulated by IFN-gamma, which likely represents the T-cell requirement in SE-mediated weight loss. Our studies thus implicate two distinct class II MHC-dependent signaling pathways for SE, the first involving direct signal transduction through class II MHC molecules mediated by either mutant or wild-type toxin and the second requiring T-cell stimulation by toxin-class II MHC complexes with consequent production of IFN-gamma. We suggest that both pathways are required for optimal monocyte TNF-alpha production in vitro and SE-induced toxicity in vivo.


Adherence of Legionella pneumophila to guinea pig peritoneal macrophages, J774 mouse macrophages, and undifferentiated U937 human monocytes: role of Fc and complement receptors.

Legionella pneumophila, the causative agent of Legionnaires' disease, is a facultative intracellular pathogen of alveolar macrophages. Although previous studies have demonstrated that specific antibody facilitates uptake of L. pneumophila by phagocytic cells, the role of complement has been unclear. Thus, we have examined the relative contributions of Fc gamma- and complement receptor-mediated adherence to guinea pig peritoneal macrophages, U937 human monocytic cells, and J774 mouse macrophage cells. Opsonization of L. pneumophila (Philadelphia 2) with polyclonal immunoglobulin G promoted maximum adherence to guinea pig macrophages. In contrast, incubation in the presence of 20% fresh nonimmune human serum from a single donor did not promote adherence. The results obtained with U937 and J774 cells paralleled those obtained with guinea pig macrophages. In the absence of specific antibody, opsonization with guinea pig complement did not enhance adherence of the Philadelphia 1, Philadelphia 2, or Knoxville strain. However, when complement was added to heat-inactivated, specific antiserum, a fourfold increase in the number of adherent organisms was observed. Blocking studies utilizing membrane receptor-specific monoclonal antibodies demonstrated that both Fc and complement receptors mediated adherence of organisms treated with complement in the presence of specific antibody. These results suggest that complement augments adherence of L. pneumophila only when acting in concert with specific antibody.


Streptococcal C5a peptidase is a highly specific endopeptidase.

Compositional analysis of streptococcal C5a peptidase (SCPA) cleavage products from a synthetic peptide corresponding to the 20 C-terminal residues of C5a demonstrated that the target cleavage site is His-Lys rather than Lys-Asp, as previously suggested. A C5a peptide analog with Lys replaced by Gln was also subject to cleavage by SCPA. This confirmed that His-Lys rather than Lys-Asp is the scissile bond. Cleavage at histidine is unusual but is the same as that suggested for a peptidase produced by group B streptococci. Native C5 protein was also resistant to SCPA, suggesting that the His-Lys bond is inaccessible prior to proteolytic cleavage by C5 convertase. These experiments showed that the streptococcal C5a peptidase is highly specific for C5a and suggest that its function is not merely to process protein for metabolic consumption but to act primarily to eliminate this chemotactic signal from inflammatory foci.


Organization of aerobactin, hemolysin, and antibacterial resistance genes in lactose-negative Escherichia coli strains of serotype O4 isolated from children with diarrhea.

Epidemiologically related, non-lactose-fermenting (NLF) Escherichia coli strains of serotype O4 have been isolated at a high frequency from children with diarrhea in Somalia (M. Nicoletti, F. Superti, C. Conti, A. Calconi, and C. Zagaglia, J. Clin. Microbiol. 26:524-529, 1988). In order to define the virulence potential of these strains, we characterized the replication properties of their high-molecular-weight plasmids and studied the genetic locations and organization of the aerobactin (aer) and hemolysin (hly) determinants encoded by 23 NLF O4 E. coli strains. Southern blot hybridizations, mobilization assays of nonconjugative plasmids, and incompatibility-exclusion experiments conducted with a conjugative incompatibility group FI (IncFI) plasmid showed that (i) 20 out of the 23 strains examined harbor a 160- to 180-kb IncFI plasmid that shares homology with the basic replicons RepFIA, RepFIB, and (except for the plasmid of one strain) RepFIC, and 22 strains also contain a 40- to 140-kb IncFII plasmid sharing homology with the RepFIIA replicon; (ii) the IncFI plasmid is nonconjugative and carries antibiotic resistance genes; (iii) the aer system is located on the IncFI plasmids and/or the chromosomes in the three strains not harboring IncFI, and it is found in an inverted orientation; (iv) the hly determinants are located on the chromosome, and their genetic organization is well conserved and closely resembles that of the reference hemolytic plasmid pHly152; and (v) Hly- mutants obtained by transposon insertion mutagenesis are not cytotoxic to HeLa cell monolayers, indicating that hemolysin is responsible for the high cytotoxic activity we have previously reported for these strains. The structural organization of the plasmid-encoded aer operon, together with the finding that those plasmids also carry antibiotic resistance genes, indicates that the IncFI plasmid of the NLF O4 E. coli strains studied more closely resembles aer-encoding virulence IncFI Salmonella R plasmids than E. coli ColV plasmids. The data presented here cannot rule out whether the strains examined are potentially intestinal or extraintestinal pathogens. Nevertheless, the genetic organization of the virulence genes, together with the epidemiological behavior and the wide spectrum of antibiotic resistance of the NLF O4 E. coli strains, indicates that these strains are structured as typical E. coli pathogenic isolates of human origin.


Histological and immunocytochemical characterization of Coxiella burnetii-associated lesions in the murine uterus and placenta.

The fetoplacental units and the postgravid uterus of BALB/cJ (H-2d) mice inoculated intraperitoneally with Coxiella burnetii (Nine Mile isolate, phase I) on day 6 of pregnancy were examined histologically and immunocytochemically at 1 to 160 days postinoculation. Clinically, abortions, stillbirths, and perinatal deaths were observed. Histological lesions in the placenta were characterized by severe necrosis of the decidua basalis and the labyrinth, fibrinoid degeneration of decidual vessels, and microthrombosis. Pyometra and endometritis at the sites of previous placental attachment, characterized by ulceration, central necrosis, and moderate cellular infiltration consisting of neutrophils and macrophages, were observed postpartum. Pups sacrificed at the age of 9 days exhibited interstitial pneumonia with few granulomas and granulomatous hepatitis and splenitis. Immunocytochemically, antigen-bearing cells were first detected in the decidua 9 days postconception, and single immunopositive cells were detected in the fetal placenta 4 days later. Thereafter, until abortion or parturition, abundant accumulation of C. burnetii antigen was observed in the maternal and fetal compartments of the placenta. Up to 28 days postinoculation, many immunopositive cells were demonstrated at the sites of previous placental attachment, whereas the adjacent endometrium contained only a few antigen-positive cells. C. burnetii antigen was demonstrated in decidual cells, trophoblasts, and macrophages and extracellularly within the sinuses of the labyrinth and in the uterine lumen but not in granulated metrial gland cells. Fetuses in utero and aborted, stillborn, or perinatally dying offspring were immunocytochemically negative for C. burnetii antigen; however, pups killed 9 days after birth showed lesion-associated positive immunoreaction in the lung, liver, and spleen. The present study shows that infection with C. burnetii during pregnancy results in uncontrolled growth of the organism in the murine uteroplacental unit and that associated lesions are characterized by necrosis of placental tissues, fibrinoid degeneration of decidual vessels, and microthrombosis.


Yersinia pestis YopM: thrombin binding and overexpression.

In previous studies, Yersinia pestis YopM has been shown through mutational analysis to be necessary for virulence in mice and found to have homology with the thrombin-binding domain of the platelet receptor GPIb alpha. In this study, YopM was purified and shown by dot blot and chemical cross-linking tests to bind to human alpha-thrombin. No cross-linked product could be detected when human prothrombin was incubated with YopM. As a functional test of thrombin binding, it was shown that native but not boiled YopM inhibits thrombin-induced aggregation of human platelets. Control tests showed that YopM did not inactivate the platelets themselves, nor was its effect a nonspecific consequence of its very acidic isoelectric point. Microsequencing of YopM revealed an intact N terminus, indicating that functional YopM is not processed at the N terminus or secreted by a mechanism involving a cleavable signal sequence. Further characterization was made of an interesting effect on yopM expression that had been noticed in a previous study. A 1.5-kb HaeIII subclone overexpressed YopM in both Y. pestis and Escherichia coli compared with a larger clone containing the 5.3-kb HindIII-F fragment. To search for a possible regulator of YopM expression, the HindIII-F fragment was sequenced, revealing several open reading frames and three large repeated sequences. Deletional analysis showed that these were not involved in regulation of yopM. The data implicated a DNA structure 5' to yopM in moderating yopM expression.


Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor alpha.

Inflammatory mediators produced by cells in the gingiva have been implicated in the initiation and progression of periodontal disease, a common infectious disease. In this study, we examined the biological activity of neutrophil chemotactic factors and the kinetics of expression of interleukin-8 (IL-8) mRNA derived from normal gingival fibroblasts in response to inflammatory mediators in an in vitro model. Gingival fibroblasts stimulated by either recombinant human interleukin-1 beta or recombinant human tumor necrosis factor alpha produced neutrophil chemotactic factors after 4 h, whereas expression of cell-derived IL-8 mRNA was detected within 1 h after stimulation. Furthermore, in a neutralization assay, rabbit anti-recombinant human IL-8 antiserum inhibited neutrophil chemotactic activity to basal levels. These results provide evidence that gingival fibroblasts synthesize potent chemotactic factors such as IL-8 in the presence of the inflammatory mediators interleukin-1 beta and tumor necrosis factor alpha. The activity of these factors may contribute to neutrophil-mediated processes in the pathogenesis of periodontal disease.


Purification and characterization of the urease enzymes of Helicobacter species from humans and animals.

The urease enzymes of Helicobacter pylori, H. mustelae, H. felis, and H. nemestrinae have been purified to homogeneity by affinity chromatography and characterized. The native urease enzymes of the four organisms were found to be almost identical, with a pI of 6.1 and molecular masses of 480 to 500 kDa, as determined by electrophoretic mobility in nondenaturing polyacrylamide gels. Transmission electron microscopy of the native urease showed it to be a molecule approximately 13 nm in diameter, with hexagonal symmetry. Denaturation studies indicated that each urease enzyme molecule was composed of two nonidentical subunits with molecular masses of approximately 64 and 30 kDa. The subunits were present in a 1:1 ratio, suggesting a hexameric stoichiometry for the native molecule. The predicted molecular mass of H. pylori urease, based on subunit molecular weight and stoichiometry, is 568 kDa. N-terminal amino acid sequencing of the enzyme subunits from the four species revealed high levels of homology. The large subunits (UreB) were found to be 92 to 100% homologous, and the small subunits (UreA) were 75 to 95% homologous over the first 12 to 20 residues. The high degree of homology suggests a common ancestral origin and an important role for the urease enzymes of these organisms.


Clonal and antigenic analysis of serogroup A Neisseria meningitidis with particular reference to epidemiological features of epidemic meningitis in the People's Republic of China.

Representative strains of serogroup A Neisseria meningitidis were chosen from all major meningitis epidemics worldwide since 1960 and subjected to analysis for the electrophoretic variation of 15 cytoplasmic allozymes and four outer membrane proteins. The 290 strains defined 84 unique electrophoretic types which were classified in nine subgroups. Tests with monoclonal antibodies specific for conserved pilin epitopes showed that the class I, IIa, and IIb epitopes were uniform within the subgroups. Similarly, the subgroups were uniform for expression of different variable regions of class 1 outer membrane protein, with a few minor exceptions. Many of the bacteria tested were isolated in the People's Republic of China, and the epidemiology of Chinese epidemics of meningococcal meningitis is described. The analysis approaches a global description of epidemic meningitis caused by serogroup A meningococci in the past 30 years.


Intestinal changes associated with expression of immunity to challenge with Eimeria vermiformis.

To provide more information on the mechanisms involved in the immune inhibition of eimeria infections, NIH mice were adoptively immunized against infection with Eimeria vermiformis by the transfer of mesenteric lymph node cells from primed animals and homologously challenged. Subsequent changes in the architecture and cellular composition of the intestine were compared with those observed in similarly challenged susceptible control mice and correlated with the development of the parasite in the two groups. Actively immunized mice were also examined. In adoptively immunized mice, the development of E. vermiformis was inhibited within 3 days of administering the challenge inoculum. Concurrent changes in the intestine included lymphocytic infiltration, crypt hyperplasia, flattening of the crypt epithelium, and a reduction in the number of Paneth cells. Hyperplasia of goblet and pyroninophilic cells in response to challenge, although accelerated and enhanced in adoptively immunized hosts, occurred after the inhibition of the parasites, and mastocytosis was not observed in these animals, findings which suggest that the activities of goblet, pyroninophilic, and mast cells were not instrumental in reducing the numbers of parasites. The intestines of immunized mice contained fewer intraepithelial lymphocytes at the time of inhibition of the parasites than did those of the controls. The protective effects and intestinal changes described above did not differ appreciably from those seen after challenge of mice that had been immunized by infection.


An 87-kilodalton glucan-binding protein of Streptococcus sobrinus B13.

An 87-kDa glucan-binding protein (GBP) of Streptococcus sobrinus B13 (serotype d) was isolated and purified from extracellular culture supernatant by using affinity chromatography on Sephadex G-50 and elution with a guanidine HCl gradient. Western blot (immunoblot) analysis showed it to be antigenically related, but not completely identical, to the 74-kDa GBP of Streptococcus mutans Ingbritt. The 87-kDa GBP has no glucosyltransferase activity. A possible role for this GBP in the cariogenicity of S. sobrinus B13 is suggested.


Frequency of antigen-specific B cells during experimental ocular Chlamydia trachomatis infection.

Chlamydia-specific antibody-secreting cells have been identified in conjunctiva and draining cervical lymph nodes by an ELISPOT assay in a cynomolgus monkey model of trachoma. These local sites contained numbers of chlamydia-specific B cells that were higher than those in distant inguinal lymph nodes and peripheral blood. The numbers of chlamydia-specific immunoglobulin G-secreting B cells observed were 5 to 57 per 10(6) cells in conjunctiva and 24 to 996 per 10(6) cells in cervical lymph nodes during conjunctival infection or after challenge of immune monkeys with the chlamydial 57-kDa heat shock protein (hsp60). These studies demonstrate a large chlamydia-specific B-cell component in the conjunctiva during ocular chlamydial infection. These results are similar to our findings for chlamydia-specific T-cell responses.


Studies with enteroaggregative Escherichia coli in the gnotobiotic piglet gastroenteritis model.

Two strains of enteroaggregative Escherichia coli of human origin fed to gnotobiotic piglets caused diarrhea or death in the majority of them. Histological examination revealed moderate hyperemia of the distal small intestine and cecum, swelling of small intestinal villi, and layers of aggregated bacteria stacked together in a mucus gel-like matrix overlying intact epithelium. These findings confirm that enteroaggregative E. coli strains produce distinctive intestinal lesions different from those caused by other major categories of diarrheagenic E. coli.


Alteration of cytoplasmic Ca2+ in resting and stimulated human neutrophils by short-chain carboxylic acids at neutral pH.

The results reported here indicate that the short-chain carboxylic acids acetate and propionate stimulate cytoplasmic calcium mobilization in human polymorphonuclear leukocytes, while butyrate and lactate do not. Together with the results of previous work, this indicates that there are at least three classes of short-chain carboxylic acids: those which can alter only cytoplasmic pH (e.g., lactic acid), those which can alter cytoplasmic pH and actin (e.g., butyric acid), and those which can alter cytoplasmic pH, actin, and calcium (e.g., acetate and propionate).


Encystation of Giardia lamblia leads to expression of antigens recognized by antibodies against conserved heat shock proteins.

During in vitro encystation, Giardia lamblia expresses several stage-specific proteins which are recognized in immunoblots by antisera raised against antigens from three different pathogens. The antigens belong to two different families of conserved stress proteins: (i) HSP60 purified from Legionella pneumophila and recombinant HSP60 from Mycobacterium bovis BCG and (ii) recombinant HSP70 from Plasmodium falciparum.


A bactericidal monoclonal antibody specific for the lipooligosaccharide of Bordetella pertussis reduces colonization of the respiratory tract of mice after aerosol infection with B. pertussis.

A mouse immunoglobulin G3 monoclonal antibody specific for the core oligosaccharide moiety of the lipooligosaccharide (LOS) of Bordetella pertussis has been shown to have complement-dependent bactericidal activity. This monoclonal antibody exhibits bactericidal activity against strains of B. pertussis that express the LOS A phenotype. In addition this monoclonal antibody was effective in reducing colonization by B. pertussis in both the lungs and tracheas of mice after aerosol infection.


Effects of duration of pressure overload on the reversibility of impaired coronary autoregulation in rats.

The aim of this study was to determine the effects of duration of pressure overload on the reversibility of impaired coronary autoregulation in hypertropied hearts. The experiments were performed on 38 anesthetized male Wistar rats aged 6 to 8 weeks. The ascending aorta was banded for 4 or 10 weeks, then in some rats the bands were removed for 4 weeks. We estimated coronary hemodynamics in a model consisting of isolated non-working hearts perfused with Tyrode's solution containing bovine red blood cells and serum albumin. Myocardial mass increased significantly in 4 and 10-week banded groups compared to controls. Four weeks after debanding in 4- and 10-week banded groups, the value returned to that of controls. Autoregulation gain was significantly lower in banded groups than in controls in the range between 50 and 100 mmHg of coronary perfusion pressure. Although the gain normalized in the debanded group after 4 weeks of banding, the value in the debanded groups after 10 weeks of banding remained less than zero between 25 and 150 mmHg of perfusion pressure. In transient flow response to a stepwise increase of perfusion pressure within the autoregulatory range, promptly increased flow was followed by more rapid and greater decrease in controls than in banded groups. The flow response regressed in the debanded group after 4 weeks of banding, while it remained unchanged in the debanded group after 10 weeks of banding. Thus, duration of pressure overload alters the regression of impaired coronary autoregulation in cardiac hypertrophy.


Serum cortisol levels predict infarct size and patient mortality.

We have investigated prospectively the serum cortisol response to acute myocardial infarction in 70 consecutive patients admitted to a coronary care unit and we have shown that the levels are significantly raised early in the course of the illness and prior to elevation of the cardiac specific enzyme fraction, creatine kinase MB. The magnitude of the cortisol response is related to the size of the ensuing infarction (rs = 0.54) as calculated from the total creatine kinase MB release (P < 0.001) and very high levels (> 2000 mumol/l) are predictive of mortality (P < 0.05). Serum cortisol levels may have a role in the early identification of myocardial infarction and in predicting those patients with a poor prognosis.


Non-invasive evaluation of cardiac abnormalities in heat stroke pilgrims.

Serial electrocardiograms as well as echocardiographic studies of 51 pilgrims suffering from acute heat stroke (mean rectal temperature 41.6 degrees C) were performed. All patients were examined immediately after cooling and 24 h later whenever possible. Regional wall motion abnormalities were detected in 9 cases (17.6%) while pericardial effusion was observed in 13 cases (25%) and asymmetrical septal hypertrophy was detected in 8 cases (15.6%). Other cardiac abnormalities included right ventricular dilatation and increased in left ventricular internal dimensions in 4 cases (7.8%), respectively. Thirteen cases (25.5%) had normal echocardiographic findings. Forty (78%) patients had sinus tachycardia while 8 cases (15.7%) showed atrial fibrillation with uncontrolled ventricular rate, and 3 (5.8%) had sinus bradycardia. Heat stroke electrocardiograms showed tracings demonstrating ST segment depression, compatible with ischaemia in 9 cases, while in 6 cases there were nonspecific T wave changes, whereas in another 4 cases the tracings demonstrated different conduction abnormalities. The collected data were analysed and compared to those of 43 control patients. The adverse effects of heat stroke on the heart are multifactorial requiring the utmost attention and understanding, as they reflect the patient's cardiovascular status.


Right ventricular volumes and hemodynamics after successful orthotopic heart transplantation. A comparison to coronary artery disease using thermodilution.

Only few data exist concerning right ventricular function in the chronic stage after cardiac transplantation. Therefore, we investigated hemodynamic and right ventricular volumetric data by a computerized thermodilution Swan-Ganz catheter in 17 patients (median age: 53, range: 18-63 yr) at a median of 24 (4 to 44) months after cardiac transplantation during rest and supine bicycle exercise. Myocardial biopsy showed grade one or less according to the classifications of Billingham. Sixteen patients with coronary artery disease, but without prior myocardial infarction, served for comparison. While angiographic left ventricular ejection fraction was nearly identical in transplant recipients [77 (60-92)%, median (range)] and in patients with coronary artery disease [78 (64-94)%], right ventricular ejection fraction was lower (p < 0.001) in patients after cardiac transplantation [37 (16-58)%] as compared to patients with coronary artery disease [56 (46-62)%]. In transplant recipients right atrial pressure was significantly higher both at rest [10 (2-18) mmHg] and exercise [18 (8-30) mmHg] than in patients with coronary artery disease [5 (1-11) and 8 (3-18) mmHg]. Pulmonary capillary wedge pressure behaved similar in both groups. To further evaluate reasons for right ventricular impairment, a correlation analysis was performed. This showed a negative correlation between right ventricular ejection fraction and the time interval after transplantation (p < 0.0002). However, there was no correlation between right ventricular ejection fraction and acute rejection or a rejection score. In conclusion, right ventricular function may be severely altered in transplant recipients, in contrast to an only slight impairment of left ventricular function.


Acute myocardial ischemia resulting in dynamic obstruction to the left ventricular outflow relieved by successful angioplasty.

A patient was admitted because of an acute myocardial infarction which evolved with heart failure and postinfarction angina. A pattern consistent with dynamic left ventricular outflow obstruction was found. It disappeared after coronary angioplasty was performed on the vessel responsible for the ischemia.


The impact of thrombolytic therapy on hospital mortality from acute myocardial infarction in the Chinese in Hong Kong.

Thrombolytic therapy using recombinant-tissue plasminogen activator, urokinase and streptokinase for acute myocardial infarction was instituted in the coronary care unit of the Prince of Wales Hospital in Hong Kong in 1988. To evaluate its impact on hospital mortality of acute myocardial infarction, the database of 465 patients (mean age 65.2 +/- 12.6 yr) admitted into the coronary care unit in the period between 1985-1990 was collected prospectively and their clinical course reviewed. Three hundred and thirty-five patients were males and 130 were females. Patients in the prethrombolytic era (1985-87) and the thrombolytic era (1988-90) were matched for age, proportion of females and clinical severity. One hundred and two patients (39.5%) received thrombolytic therapy. The overall hospital mortality (18.6%) in the thrombolytic era and that for each sex (18.2% in the males; 19.5% in the females) were significantly lower than those of prethrombolytic era (27.1%, 23.4% and 37.7%, respectively). No death was due to bleeding complication. The benefit of thrombolytic therapies in the Chinese was confirmed. More effort is needed to popularize this concept in the Chinese communities, to shorten the prehospital delay of patients and to extend its utilisation to the elderly patients.


Effect of diltiazem on silent ischemic episodes, plasma bradykinin and prostaglandin metabolism.

Plasma bradykinin and prostaglandin metabolism are related to the anginal pain modulating system in patients with ischemic heart disease. We carried out a placebo controlled single blind test of diltiazem (30 mg three times a day) in 15 patients with chronic stable angina. The effect of diltiazem was evaluated by exercise treadmill testing and 48-h ambulatory electrocardiographic monitoring. Plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels were determined by radioimmunoassay prior to and during diltiazem therapy. Diltiazem significantly increased the exercise time and reduced episodes of angina. Diltiazem, however, did not appreciably improve either the frequency of silent myocardial ischemic episodes or the total duration of the silent myocardial ischemic episodes. Diltiazem also tended to decrease plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels. When ischemic episodes on ambulatory electrocardiographic monitoring are categorized according to heart rate change at the onset of episode (type A, preceded by heart rate increase > or = 5 beats/min; type B, no preceding heart rate increase), diltiazem was only effective on type A ischemic episodes as well as on symptomatic ischemia. Further, bradykinin was significantly decreased by diltiazem only in patients with exercise-induced silent ischemia or no exercise-induced ischemia, while the thromboxane B2/6-keto-prostaglandin F1 alpha ratio was unaffected by the administration of diltiazem. Thus, silent and symptomatic ischemia may be associated with different bradykinin and prostaglandin responses.


Prodromal chest pains: clues to the pathogenesis of non-Q wave acute myocardial infarction?

Prodromal chest pains were recorded from consecutive admissions to a single coronary care unit and the symptoms of those with Q wave and non-Q wave acute myocardial infarction were compared. Of 809 admissions there were 201 with Q wave ad 88 with non-Q wave infarction. The non-Q wave infarction group was older, included more women and a greater proportion had suffered a previous myocardial infarct. Effort angina was equally common in both groups, but in the Q wave infarction group, angina was more often of recent onset, within the previous 4 weeks. Symptoms to indicate worsening angina, more prolonged, intense or frequent pain, were equally common in both groups. These findings suggest that although the extent of coronary artery disease may differ, Q wave and non-Q wave myocardial infarction share a common pathogenic mechanism.


Thrombolysis following pre-hospital cardiopulmonary resuscitation.

Forty-eight patients were discharged from hospital following successful resuscitation from out-of-hospital ventricular fibrillation. Sixteen of these patients received intravenous thrombolytic therapy on admission to hospital. There were 3 significant bleeding complications and 2 cases of inappropriate administration of streptokinase. One of the patients that did not receive thrombolysis also had a significant bleeding complication of cardiopulmonary resuscitation. Patients admitted to hospital following resuscitation should only receive thrombolytic therapy when there is overwhelming electrocardiographic evidence of acute myocardial infarction, and even then with caution.


Radiofrequency catheter ablation for treatment of Wolff-Parkinson-White syndrome--short- and long-term follow-up.

One hundred and twenty-five patients with accessory pathways mediated tachyarrhythmias underwent radiofrequency ablation. Right-sided accessory pathways were ablated from the atrial aspect of the tricuspid anulus (all from the femoral vein approach) and the left-sided accessory pathways were ablated from the atrial or ventricular aspect of the mitral anulus. Immediately after the procedures, 3 of 8 accessory pathways (38%) and 131 of 137 accessory pathways (95%) were ablated successfully with radiofrequency through a small-tip (2 mm) and a large-tip (4 mm) electrode catheter, respectively. Seven of the 11 accessory pathways that failed radiofrequency ablation had a later successful direct current ablation. During follow-up (3 to 22 months), serial electrophysiological study showed that 11 of the 114 patients (10%) with successful ablation had return of accessory pathway conduction (2 had recurrence of tachycardia, 2%). Complications included accidental AV block (1 patient), cardiac tamponade (1 patient) and possible aortic dissection (1 patient). Transient proarrhythmic effects (more atrial and ventricular premature beats) were seen during the first week and sustained ventricular tachyarrhythmias were not inducible. In a successful session, procedure and radiation exposure times (including the time for diagnostic procedures) were 3.8 +/- 0.2 h and 45 +/- 4 min, respectively. This study confirms that radiofrequency ablation with a large-tip electrode catheter is an effective and relatively safe nonsurgical method for treatment of Wolff-Parkinson-White syndrome, with a low complication and recurrence rate.


Acute and chronic performance of a steroid eluting electrode for ventricular pacing.

Studies have demonstrated consistently low stimulation thresholds in the first months following implantation of steroid eluting electrodes. There have been no reported cases of exit block. There is little information on the long-term performance of these leads. Data were collected on 15 patients in whom Medtronic steroid eluting leads (5023 and 4003) had been implanted in 1987. Stimulation thresholds were measured at implantation and at weeks 1, 2, 3, 4, 5, 6 and 12. Stimulation threshold, lead impedance and sensing thresholds were monitored periodically for 3 yr using the telemetered function of the pulse generator. Three-month follow-up was obtained in all the patients and 3-yr follow-up in 10. Stimulation thresholds remained low throughout the follow-up period in all but one patient who developed exit block necessitating the replacement of the pacing system. In the remaining patients there was a significant increase in mean stimulation threshold from implantation to week 1 (mean stimulation threshold at implantation = 0.106 ms, mean ST at week 1 = 0.182 ms; p = 0.05), and also a gradual increase in the stimulation threshold over the first 2 yr of follow up (mean stimulation threshold 1 week = 0.182 ms, mean stimulation threshold months 13-24 = 0.243 ms; p = 0.05). Lead impedance showed no significant change over the follow-up period (mean change in impedance = 4.3 omega, SD 163.2, p = 0.97). Unlike many conventional electrodes, steroid eluting leads show no early peak in stimulation threshold but exit block can occur. Stimulation thresholds show a small but significant rise over time.


Biophysical parameters of radiofrequency catheter ablation.

Radiofrequency catheter ablation has been shown to be an effective treatment for patients with accessory pathways in Wolff-Parkinson-White syndrome and other supraventricular tachycardias. However, the biophysical parameters used so far in vivo did not correlate to the size of myocardial lesions and provided no information about the myocardial wall contact of the electrode. In this study 104 radiofrequency applications were performed on excised pig myocardium in circulating heparinized pig blood as well as in blood alone, and root mean square (rms) voltage, root mean square current and phase angle were measured using a specially developed device. The calculated effective power and output power differed by only 2-7% when measured at the point of maximum current during coagulation. A drop of current following a rise in impedance led to a phase displacement of more than 80 degrees and thereby to a drop of effective power to 17% of the output power. Hence, apparent output power consists mainly of ineffective power. The time dependent variations of phase angle, impedance and current were found to be useful for distinguishing between the media blood and myocardium. These results show that physical parameters measured during radiofrequency catheter ablation may help to control electrode position in the clinical situation and reduce the number and duration of ineffective energy applications.


Left ventricular function response to exercise in normotensive obese subjects: influence of degree and duration of obesity.

This study has been designed to evaluate whether duration and severity of obesity can influence left ventricular function response to exercise in obese subjects without other known cardiovascular risk factors such as hypertension, diabetes or hyperlipoproteinemia. A total of 29 obese subjects were included and they were divided, according to their body mass index and to Garrow's criteria as follows: Overweight or mildly obese subjects: body mass index from 25 to 30 kg/m2; moderately obese subjects: body mass index > 30 and < 40 kg/m2. Both obese groups were further subdivided according to their duration of obesity evaluated by accurate anamnesis in subgroup A (duration of obesity less than 120 months) and subgroup B (duration of obesity more than 120 months). Left ventricular ejection fraction was detected by blood pool gated radionuclide angiocardiography both at rest and after symptom-limited bicycle ergometer procedure. At peak exercise left ventricular ejection fraction increased significantly (p < 0.05) only in overweight subjects. Exercise produced an increase of left ventricular ejection fraction in 14 overweight and in 5 moderately obese subjects and a decrease in 2 moderately obese subjects. At peak exercise mean heart rate and mean blood pressure increased significantly (p < 0.001) in both groups. When obese subjects were subgrouped according to duration of obesity, left ventricular ejection fraction increased significantly (p < 0.05) only in overweight subjects with duration of obesity less than 120 months. Duration of obesity correlated inversely with percent change in left ventricular ejection fraction (EF) at peak exercise (delta EF) (r = -0.59; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Antihypertensive effects of low doses of hydrochlorothiazide in hypertensive black Zimbabweans.

The antihypertensive effects of low doses of hydrochlorothiazide have not been examined in black African hypertensive patients although hydrochlorothiazide is commonly used as first-line therapy. The antihypertensive effects of hydrochlorothiazide in a daily dose of 6.25, 12.5, 25 and 50 mg were examined in 19 black Zimbabwean hypertensive patients in a double-blind, random order, placebo-controlled, cross-over trial. The mean systolic blood pressure on placebo was 170.2 mmHg (95% CI +/- 9.0 mmHg) and on daily doses of hydrochlorothiazide decreased to: 161.1 mmHg (95% CI + 10.0 mmHg) on 6.25 mg; 156.6 mmHg (95% CI +/- 8.6 mmHg) on 12.5 mg; 154.9 mmHg (95% CI +/- 8.5 mmHg) on 25 mg and 149.1 mmHg (95% CI +/- 9.2 mmHg) on 50 mg. The mean diastolic blood pressure on placebo was 101.4 mmHg (95% CI +/- 5.0 mmHg) and decreased to: 98.0 mmHg (95% CI +/- 5.7 mmHg) on 6.25 mg; 96.1 mmHg (95% CI +/- 4.5 mmHg) on 12.5 mg; 93.6 mmHg (95% CI +/- 5.3 mmHg) on 25 mg and 90.5 mmHg (95% CI +/- 3.9 mmHg) on 50 mg. Hydrochlorothiazide in doses of 25 mg and 50 mg decreased systolic and diastolic blood pressure and the 12.5 mg dose decreased systolic blood pressure significantly more than placebo. We conclude that in this population maximum antihypertensive effect is not seen with the lower doses of hydrochlorothiazide and 25 mg is an appropriate starting dose for most patients.


Echocardiographic variables affecting surgical outcome in patients undergoing closed mitral commissurotomy.

We studied, by transthoracic cross-sectional echocardiography, the influence of subvalvar pathology on the early hemodynamic result of closed mitral commissurotomy in 132 patients with severe rheumatic mitral stenosis (56 males, 76 females, mean age 25.2 yr, range 10-55) in our tertiary care hospital in North India from July 89 to December 91. The mitral subdistance ratio was calculated by dividing the distance between the papillary muscle tip and mitral valve in systole (apical 4-chamber view) by left ventricular diastolic length (apical long axis view). Nineteen patients with mild subvalvar pathology (mitral subdistance ratio > 0.18) and 71 patients with moderate, achieved a larger valve area (2.26 cm2 SD 0.54) than 42 patients with severe subvalvar pathology (mitral subdistance ratio < 0.12, postoperative valve area 2.09 cm2 SD 0.6, p < 0.05). In addition, 9 of these 42 patients (21%) developed significant mitral regurgitation (4 deaths), in contrast to 1/19 with mild and 6/71 with moderate subvalvar pathology. We conclude that echocardiography identifies patients with severe subvalvar pathology who fare poorly after closed mitral commissurotomy. However, this procedure would still be practised in developing countries like ours due to financial constraints.


Simultaneous measurement of left atrial pressure by Doppler echocardiography and catheterization.

Simultaneous, continuous wave Doppler echocardiography, left ventricular systolic and mean pulmonary capillary wedge pressure measurements were performed during cardiac catheterization in 54 patients with mitral regurgitation. Doppler-derived left atrial pressure, which was calculated by subtracting mitral regurgitant gradient from brachial artery systolic pressure, correlated well with mean pulmonary capillary wedge pressure by catheter (r = 0.933, SEE = 2.9 mmHg, P < 0.001); a comparison between non-invasive and invasive systolic gradients across the mitral valve yielded a high correlation (r = 0.91, SEE = 6.0 mmHg, P < 0.001); and there was also a high correlation between brachial artery and left ventricular systolic pressures (r = 0.93, SEE = 4.9 mmHg, P < 0.01). It is concluded that Doppler echocardiography provides a reliable and accurate method for complete non-invasive assessment of left atrial pressure in patients with mitral regurgitation.


Left-atrium-to-right-ventricle shunting after surgery for atrioventricular septal defect: an unusual sequel detected by transesophageal echocardiography.

A 25-yr-old female who had undergone surgery for common atrium and atrioventricular septal defect at the age of 9, was found to have residual shunting at the level of the atrioventricular junction. Precordial echocardiography failed to assess the direction of the shunt. Transesophageal echocardiography showed dehiscence of the atrial patch at the level of the atrioventricular junction. Through this defect left-atrium-to right ventricle shunting occurred in diastole, whereas in systole the defect was closed by the juxtaposition of the anterior tricuspid valve leaflet.


Right atrial thrombus in constrictive pericarditis.

We describe right atrial thrombus complicated by tricuspid valve obstruction in a patient with constrictive pericarditis. This report highlights the role of surgical thrombectomy, and the investigation of constrictive pericarditis to exclude intra-cardiac thrombus.


Hypoplastic right ventricle with mild pulmonary stenosis in an adult.

A rare cyanotic heart disease surviving to adulthood with minimal symptoms is presented. The final diagnosis was hypoplastic right ventricle with mild pulmonary stenosis, where the latter was not responsible for the right-to-left shunting across a large atrial septal defect. The differences from cases reported in the literature are highlighted.


Multichamber intracardiac thrombi in a patient without any predisposing cardiac or non-cardiac disease.

A patient who developed multichamber (left ventricle, right ventricle, right atrium) intracardiac thrombi without having any predisposing cardiac or non-cardiac disease is discussed. The thrombi were diagnosed echocardiographically and confirmed histopathologically. The occurrence of multichamber mural thrombi without any predisposing disease is extremely rare. Risk factors for their development have been reviewed.


Coping and maintenance strategies of spontaneous remitters from problem use of alcohol and heroin in Switzerland.

A short review of the literature is followed by data from a Swiss study on spontaneous remission from problem use of alcohol and heroin conducted in 1988. The analysis of the collected life histories led to the identification of a motivation phase, a stage of decision implementation, and a struggle for maintenance as the major sequence of the autoremission process. The discussion focuses on the "tools" which remitters use to put their decision into practice. The coping mechanisms identified are "diversion," "self-monitoring," and "distancing." In relation to the maintenance phase, the perception of possible relapse situations and intuitive predictions of the subjects and collaterals are analyzed.


Alcohol-related problems encountered by Japanese, Caucasians, and Japanese-Americans.

Using population-based survey data, personal-problematic and socioproblematic factors were examined among Japanese in Japan, Japanese-Americans in Hawaii, and Japanese-Americans; Caucasians in California were analyzed as a control group. Caucasian males were more likely to exhibit drinking-related social problems, whereas Japanese males showed more personal-problematic symptoms. Japanese-American men, both in Hawaii and California, were least likely among the three ethnic groups to have personal-problematic symptoms and were more likely to have socioproblematic symptoms than Japanese men. These differences might be explained by differences in the perception of social problems.


Voluntary agencies dealing with drug and alcohol misusers: a comparison of three surveys conducted in London, Scotland, and Tasmania.

A comparison is presented of three independent surveys of voluntary agencies dealing with drug misusers in London, Scotland, and Tasmania. The comparison shows that in all three locations: (1) agencies demonstrate a recent and rapid growth, are predominantly small and rely on the commitment of a few workers, are heavily dependent on government funding and most funds are spent on salaries; (2) staff are largely unqualified and recently appointed, see their primary activity as counseling; and (3) clients are predominantly male. The community base of these agencies means wide variability in type of agency and creates problems in assessing success and in developing relationships between them and agencies in the statutory sector.


Behavioral characteristics of seroconverted intravenous drug users.

A total of 440 participants (218 in 1987 and 222 in 1988) were recruited from methadone maintenance clinics in New York City. After obtaining informed consent, a standardized questionnaire was administered. Also, sera were collected and tested for HIV antibody. The overall HIV infection rate was 60% in 1987 and 52% in 1988. In 1987 and 1988, respectively, 19 of 23 and 23 of 40 participants who admitted to a previous HIV seronegative result were found to test HIV seropositive. The behavioral factors which differentiated suspected seroconverters from participants who remained seronegative were frequencies of sharing needles (p < .01), sharing cookers (p < .02), and use of shooting galleries (p < .05) during the last 5 years. Needle-sharing behaviors continue to be associated with HIV seroconversion among IVDUs. More effective education to stop needle sharing among IVDUs is needed.


Outpatient care participation and six-month status: results with an inner city impoverished alcoholic veterans population.

One hundred and thirty-seven impoverished, inner city, predominately Black alcoholic veterans were divided into four groups based on the frequency of their attendance at an outpatient clinic. They were assessed 6 months after their joining the clinic. In general, many variables reflecting lessened alcohol consumption were connected with greater amounts of clinic attendance. In most instances a month or more of attendance at the clinic appeared necessary before the positive changes started to occur.


Mortality associated with drug misuse among blacks in New York City, 1979-1981.

A comparison of age-specific death rates from "drug dependence" (ICD 304) among Blacks and Whites in New York City for 1979-1981 found two distinct patterns of mortality. Blacks have higher levels of mortality which extend from the central adult years into middle age while deaths among Whites are confined largely to the younger years (below 35). Among both racial groups, mortality is much higher for males than for females. When male undercount is "corrected," the ratios between male and female deaths are smaller. The difference in economic opportunities for Whites and Blacks is suggested as a reason why Whites "age out" of the years of highest risk before Blacks.


Violence and illegal drug use among adolescents: evidence from the U.S. National Adolescent Student Health Survey.

The relationships between violence, drug use, and victimization were examined in a representative sample of American adolescents. The commonly used illegal drugs (marijuana, amyl/butyl nitrites, psychedelics, amphetamines, and cocaine) and alcohol were considered. Drug users, compared to nonusers, fought more, took more risks which predisposed them to assault, and were assaulted more both at school and outside school supervision. Adolescents who were victims at school were also more likely to be victimized outside of school supervision. This study clearly demonstrates that the aggressor may also be the victim, and that illegal drug/alcohol use is related to victimization.


Does the codependent encourage substance-dependent behavior? Paradoxical injunctions in the codependent relationship.

It is argued that the paradoxical nature of the power structure within the codependent relationship places limits on the types of control strategies that codependents can utilize in their attempts to extinguish their partner's substance-dependent behavior. From a social exchange and learning theory perspective, it is argued that the types of control strategies that codependents utilize are not only ineffective, but they actually operate to strengthen the likelihood that substance misuse will be repeated in the future. Types of communication behaviors that codependents utilize in order to control are considered, along with ensuing implications for intervention.


Alcohol and other drug use among adolescents with disabilities.

This study assessed the incidence rates of alcohol and other drug (AOD) use among a sample of five groups of adolescents: (1) nondisabled students, (2) learning disabled students, (3) behaviorally disordered/less aggressive students, (4) behaviorally disordered students, and (5) behaviorally disordered/self-contained students. The learning disabled, behaviorally disordered/less aggressive, and nondisabled students reported similar AOD use rates. The behaviorally disordered/self-contained students reported substantially more AOD use than the other groups. The behaviorally disordered students reported higher usage of some AODs, but the differences were not as dramatic as those of the behaviorally disordered/self-contained group.


Effects of sodium valproate on the immune response.

The effects of long-term treatment with sodium valproate (VAL) on humoral immunity (Jerne plaque assay) and the delayed-type hypersensitivity (DTH) response of mice were studied. The resistance of treated animals to bacterial infection was also investigated. Various doses of sodium valproate were administered intraperitoneally (on alternate days) for periods of 1, 3 and 7 weeks. Although treatment for 1 week produced no significant effect, VAL treatment (50 and 150 mg/kg/48 h) for periods of 3 and 7 weeks resulted in enhanced numbers of plaque-forming cells (PFC) per spleen and increased spleen weights (after 3 weeks treatment). In contrast, VAL pretreatment of spleen cells in vitro was without effect. Also, no effect of VAL on DTH was observed after 1 or 3 weeks treatment (150 mg/kg/48 h).


Anticomplementary activity of boswellic acids--an inhibitor of C3-convertase of the classical complement pathway.

Boswellic acids (BA), an anti-inflammatory and anti-arthritic principle/s of Boswellia serrata, were found to possess anticomplementary activity. It inhibits the in vitro immunohaemolysis of antibody-coated sheep erythrocytes by pooled guinea-pig serum. The reduced immunohaemolysis was found to be due to inhibition of C3-convertase of the classical complement pathway. The threshold concentration for inhibiting C3-convertase was found to be 100 micrograms. However, higher concentrations of BA showed constant inhibitory effects on immunohaemolysis. BA also exhibited weak inhibitory effects on individual components of the complement system. In vivo administration of BA also showed the inhibitory effect on guinea-pig serum.


Modification of spleen cell subsets by chronic cocaine administration and murine retrovirus infection in normal and protein-malnourished mice.

We have developed an experimental mouse model to study the effect of daily cocaine administration on the immune system during an acquired immune deficiency syndrome (AIDS). Mice were infected with LP-BM5 murine leukemia virus, a retrovirus which causes immunosuppression with the development of functional murine AIDS. Increasing doses of cocaine given by daily intraperitoneal injection for 11 weeks reduced body weight. A daily cocaine injection in some mice as well as a saline injection in others showed a decrease in the percentage of Thy 1.2+, CD4+ and CD8+ cells, while both treatments increased the percentage and absolute numbers of B-cells per spleen. Saline and cocaine treatment induced an increase in gamma-IFN and TNF-alpha production by splenocytes. Cocaine treatment favored a decrease in sIL-2R secretion. Saline and cocaine treatment had slightly different effects on the splenocytes of protein-malnourished mice. Cocaine treatment induced an increase in the percentage of CD8+ cells. Saline and cocaine treatments decreased the number of Mac 1+ cells in the spleen. Moreover, saline- and cocaine-treated protein-malnourished mice splenocytes did not present the increase in gamma-IFN production as well-nourished mice splenocytes showed. Retrovirus-infected mice showed a decrease in the percentage of Thy 1.2+ and CD8+ cells and an increase in the percentage and absolute numbers of CD4+, IL-2R+, Mac 1+ and B-cells. Cocaine partially prevented the enlargement of lymphoid organs due to lymphoid cell proliferation induced by murine retrovirus infection, but had little effect on the elevated percentage of CD4+ cells or B-cells or the depressed numbers of CD8+ cells associated with virus infection. However, cocaine did reduce the number of activated IL-2R+ cells and macrophages (Mac 1+) in addition to reducing the total number of cells per spleen in all subsets in retrovirus-infected mice, but not in uninfected controls. Cocaine treatment and retrovirus infection alone or in combination suppressed the release of sIL-2R into supernatant fluid during in vitro culture of splenocytes. These data illustrate that cocaine treatment modulates cell proliferation in retrovirus-infected mice and thus modifies the absolute number of cells in those subsets already altered by retrovirus infection. Retrovirus-infected and retrovirus-infected cocaine-treated protein-malnourished mice showed similar results.


Drug-induced modulation of IL-2 production in experimental murine trypanosomiasis.

In this study we evaluated the effects of N-acetyl-cysteine and indomethacin in restoring IL-2 producing ability in vitro of splenocytes from mice infected with Trypanosoma equiperdum. Spleen cells from these mice were found to produce significantly lower levels of interleukin-2 (IL-2) in response to mitogen stimulation than spleen cells from uninfected control mice. This was accompanied by considerable suppression of IL-2-receptor expression, which was not attributable to the elimination of a particular T-cell subset. Impairment of IL-2 production was not due to a primary defect in L3T4+ T-cells, but rather to the presence of both adherent and non-adherent suppressor cells that apparently acted via prostaglandin-independent and dependent mechanisms. In fact, the IL-2-producing ability of lymphocytes from infected mice could be efficiently restored by in vitro exposure to N-acetyl-cysteine or indomethacin.


Suppression of T-lymphocyte proliferation by sulphonamide hydroxylamines.

Hypersensitivity adverse drug reactions, characterized by fever and multi-organ involvement, are the most severe adverse reactions to sulphonamides. Although there is evidence that these reactions are initiated by metabolic events, these reactions appear to be propagated on an immune basis. We investigated the effect of a sulphonamide reactive metabolite, the hydroxylamine of sulphamethoxazole (SMX H/A), on the ability of T-lymphocytes to respond to stimulation with mitogens. Peripheral blood mononuclear cells (PBMCs) were collected and incubated with SMX H/A in increasing concentrations. PBMCs were then incubated with phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) or with PHA and ionomycin. T-lymphocyte proliferation was then determined by tritiated thymidine uptake. The hydroxylamine of sulphamethoxazole produced a concentration-dependent decrease in T-lymphocyte proliferation; this decrease was significant even at concentrations of hydroxylamine that were not associated with a decrease in cell viability. PBMCs incubated with SMX H/A that were washed and then added to fresh PBMCs failed to inhibit the proliferation of fresh PBMCs. The hydroxylamine of sulfamethoxazole produces profound suppression of T-lymphocyte proliferation. This suppression appears to be a direct event and does not involve the activation of suppressor cells. These findings may explain the infectious complications contributing to mortality associated with sulphonamide hypersensitivity reactions.


Selective inhibition of T-cell-dependent immune responses by bisbenzylisoquinoline alkaloids in vivo.

The bisbenzylisoquinoline (BBI) alkaloids, chondocurine, tetrandrine, isotetrandrine and cepharanthine, were tested for immunosuppressive activity in mice. A plaque-forming cell (PFC) response to a T-cell-dependent antigen, sheep red blood cell, was significantly suppressed by a 7 day treatment of chondocurine or tetrandrine at 1 mg/kg/day and of isotetrandrine at 50 mg/kg/day, but not suppressed by cepharanthine treatment. The suppressive effect of chondocurine was greater when it was given after immunization rather than before or concurrently. However, it did not affect the PFC response to a T-cell-independent antigen, lipopolysaccharide. A delayed-type hypersensitivity was also suppressed by chondocurine treatment. There was no significant change in lymphocyte number and proportion of T-cell subsets in the BBI alkaloid-treated mice. These data suggest that there is selective inhibition by chondocurine and tetrandrine of the T-cell-dependent immune reactions.


Immunomodulatory effects of neem (Azadirachta indica) oil.

Immunomodulatory effects of neem oil were studied in mice. The animals were treated intraperitoneally (i.p.) with neem oil; control animals received the emulsifying agent with or without peanut oil. Peritoneal lavage, collected on subsequent days, showed a maximum number of leukocytic cells on day 3 following treatment with neem oil; peritoneal macrophages exhibited enhanced phagocytic activity and expression of MHC class-II antigens. Neem oil treatment also induced the production of gamma interferon. Spleen cells of neem oil-treated animals showed a significantly higher lymphocyte proliferative response to in vitro challenge with Con A or tetanus toxoid (TT) than that of the controls. Pre-treatment with neem oil, however, did not augment the anti-TT antibody response. The results of this study indicate that neem oil acts as a non-specific immunostimulant and that it selectively activates the cell-mediated immune (CMI) mechanisms to elicit an enhanced response to subsequent mitogenic or antigenic challenge.


Immunotoxicity of subchronic versus chronic exposure to aldicarb in mice.

In this study we compared the immunotoxicity of subchronic vs chronic exposure to the aldicarb insecticide at a relatively low, 0.1-10 ppb, level in drinking water. The immunotoxicity of aldicarb was evaluated in 28- and 90-day studies by determination of the humoral, cellular and nonspecific immunity in inbred C57BL/6 mice. Quantification of splenic plaque-forming cells (PFC) to sheep erythrocytes (SRBC), mitogen activation of spleen lymphocytes, mixed lymphocyte reaction (MLR) and the cytofluorometric assay of the phagocytic uptake of fluorescent beads were among the parameters studied. Neither the cell viability nor the splenic cell count was affected by the insecticide exposure. Immunophenotyping and cytometric determination of L3T4+, Lyt2+ and Ig+ cells revealed no effect of the insecticide exposure on the total count of cell subsets in the ungated splenocyte population. However, a marked shift in the percentages of L3T4+ and Lyt2+ cells was noted after subchronic exposure to 1 and 10 ppb aldicarb, possibly indicating activation of these splenic T-cell subsets. Subchronic aldicarb exposure significantly suppressed the splenic PFC response to SRBC at 1 ppb dose, however, no dose-effect correlation could be concluded. Similarly, no dose-effect correlation was observed for subchronic aldicarb-related changes in mitogen responses. Subchronic exposure to aldicarb had no statistically significant effect on the mixed lymphocyte reaction (MLR) or on the macrophage phagocytosis. Chronic exposure to 0.1-10 ppb aldicarb did not affect any of the parameters measured, including the cell subsets. Thus, aldicarb-related changes in immune parameters, noted after a 28-day exposure, were compensated over chronic exposure to the insecticide.


Cocaine augments proliferation of human peripheral blood T-lymphocytes activated with anti-CD3 antibody.

Previously we observed that cocaine can suppress the phytohemagglutinin-induced proliferation of cultured, purified human T-lymphocytes. However, because the receptor activation pathways stimulated by this mitogen are not fully understood, we decided in the present study to examine the effects of cocaine on T-lymphocyte cultures stimulated with the anti-CD3 antibody which is known to stimulate these cells through the T-cell receptor complex. The results show that cocaine augments T-lymphocyte proliferation to anti-CD3 stimulation at drug concentrations observed in the blood of cocaine abusers. This augmentation was dose dependent reaching a plateau at a concentration above 0.75 microM. The amount of interleukin-2 (IL-2), as measured by ELISA, in the supernatants of T-cell cultures and the level of cytosolic free-calcium (Ca2+) mobilization in the T-cells were also increased at approximately the same concentrations that increased proliferation. Cocaine treatment alone had no effects on proliferation, IL-2 production, or Ca2+ mobilization. These results suggest that cocaine augments proliferation of human T-lymphocytes when the cells are activated through the T-cell receptor complex by increasing cytosolic Ca2+ mobilization and subsequent IL-2 production.


Effects of 2-mercaptoethanol and buthionine sulfoximine on cystine metabolism by and proliferation of mitogen-stimulated human and mouse lymphocytes.

Cysteine is an essential amino acid for lymphocytes and its anabolic products are intimately involved in lymphocyte activation. The purpose of this study was to assess the uptake and subsequent utilization of cyst(e)ine by mitogen-stimulated human peripheral blood mononuclear cells (PBMC), to evaluate the effect of an exogenous thiol, 2-mercaptoethanol (2ME), on these processes, and to compare human and mouse lymphocyte reactivities. Unlike mouse lymphocytes, the proliferation of human T-cells was inhibited by addition of 2ME although 2ME enhanced cystine uptake. Optimal responses to T-cell mitogens (Con A and PHA) were obtained with a cystine concentration of greater than or equal to 25 and 200 microM for human and mouse cells, respectively, and 2ME enhanced DNA synthesis of Con A-stimulated mouse cells regardless of the cystine dose; however, 2ME enhanced the response of human cells only in the presence of suboptimal doses of cystine. To assess whether 2ME's inability to enhance human PBMC responses was related to their glutathione (GSH) content, the human PBMC were pretreated with buthionine sulfoximine (BSO, an inhibitor of GSH synthesis). Even when the initial intracellular GSH concentration was lowered to below that of mouse lymphocytes, 2ME still inhibited proliferation. In contrast, addition of 2ME to human PBMC maintained in the presence of BSO enhanced the proliferative response suggesting that a critical level of thiols is needed for proliferation. The ability of 2ME to enhance proliferative responses in cystine deficient medium supports this contention. Consistent with thiol involvement in activation, Con A increased [35S]cystine uptake 2-fold within 4 h of incubation and enhanced subsequent conversion of cystine into cysteine and GSH. Interestingly, BSO treatment only slightly inhibited Con A-induced protein synthesis (5%), but it significantly suppressed conversion of cystine into cysteine or GSH (80-95%) and blocked DNA synthesis (90%). Overall, the results indicate that various differential thiol characteristics must exist between human and mouse lymphocytes and that a reducing equivalent is necessary for DNA synthesis but not lymphocyte activation.


Normal development of lymphokine activated killing (LAK) in peripheral blood lymphocytes from hyperprolactinemic patients.

The effect of prolactin on the interleukin 2 (IL2)-driven development of Lymphokine Activated Killing (LAK) by normal PBL and by PBL from hyperprolactinemic patients was investigated. Concentrations of PRL corresponding to the physiological serum levels of the hormone and to the Kd of the PRL receptors on NK cells (6-20 ng/ml, 0.3-1 nM) had no effect on the generation of LAK activity by normal PBL, whereas 100-200 ng/ml were slightly, although significantly, inhibitory. By contrast, PBL from 16 hyperprolactinemic patients developed levels of LAK activity comparable with those generated by PBL from age- and sex-matched normoprolactinemic donors.


Experimental model of autoimmune hemolytic anemia induced in mice with levodopa by intraperitoneal injection or oral feeding.

In this paper we describe a murine experimental model of autoimmune hemolytic anemia induced with multiple injections or oral feeding of levodopa. Strain A mice were intraperitoneally injected or fed with levodopa, at a dose equivalent to the one used in human therapy, and subsequently they developed cycles of IgM, IgG and IgA anti-mouse red blood cells (MRBC) autoantibody responses. Levodopa injection induced serum IgM and IgG anti-MRBC responses and levodopa feeding enhanced the serum anti-MRBC IgA response. The appearance of autoantibodies in the serum was followed by binding of the autoantibodies to mice erythrocytes and three phases of anemia. Red cell bound IgM and IgG autoantibodies were predominant in levodopa-injected mice whereas red cell bound IgA autoantibodies were predominant in levodopa-fed mice. The specificity of the serum IgA autoantibody was not restricted since it interacted with erythrocytes of various species.


Potentiation of immune responses in mice by a new inosine derivative--methyl inosine monophosphate (MIMP).

Inosine 5'-methyl monophosphate (MIMP) is a new immunomodulator designed to improve upon the activity of other thymomimetic purines. In Balb/c mice, MIMP was assessed for toxicity and activity on immune responses. The lethal dose for half the mice (LD50) exceeded 500 mg/kg of body weight by both the parenteral and oral routes. At doses of 1-100 mg/kg, the mice showed no visible untoward effects. The antibody response of splenocytes to sheep erythrocytes (SRBC) was measured by IgM plaque-forming cells (PFC) in soft agar under optimal conditions of immunization and challenge. MIMP (1-100 mg/kg) was given by both the intraperitoneal and oral routes (gavage) at the time of SRBC injection and 4 days thereafter. The PFC response was found to be significantly augmented. The maximum effect (approximately 2x) was observed at 50 and 100 mg/kg, via intraperitoneal (i.p.) and oral routes, respectively. Increases (maximally 1.5x) in the responses of splenic lymphocytes to mitogen stimulation with phytohemagglutinin (PHA) and concanavalin A (Con A) were observed under similar conditions of MIMP treatment. SRBC-induced delayed-hypersensitivity (DTH) was also measured under optimal conditions. By both i.p. and oral routes, enhancement of DTH response was produced by the lower doses of MIMP (0.01-1 mg/kg). Again, a second peak of optimum stimulation of DTH response was produced by 50 mg/kg of MIMP when administered by both routes. The effect was observed mainly on the sensitization rather than on the expression phase. MIMP qualifies as an effective immunopotentiator in normal mice.


Identification of immunoreactive forms of thymosin alpha 1 in serum and supernatants by combining HPLC and RIA.

Thymosin alpha 1 (T alpha 1) is a biologically active peptide, originally isolated from the thymus and currently undergoing clinical trials as an immunomodulator in cancer patients, in individuals with chronic active hepatitis, and as an immunoenhancer of vaccines in immunocompromised individuals. Absorption of rabbit antibody to thymosin alpha 1 with a synthetic C-14 fragment of T alpha 1 results in an antiserum with increased affinity for the amino terminal region of T alpha 1 and the precursor protein prothymosin alpha (ProT alpha). Using HPLC methodologies, the predominant form of immunoreactivity in serum and thymus was T alpha 1 not the precursor. Using this assay we detected a decline in mouse serum T alpha 1 following irradiation but not thymectomy, an observation consistent with the existence of an important radiation sensitive lymphoid source of serum T alpha 1. The secretion of authentic T alpha 1 but not the precursor into culture medium by thymic epithelial cells as well as in mitogen-stimulated peripheral blood lymphocytes was also demonstrated by HPLC/RIA. HPLC analysis by molecular weight sizing columns demonstrated that unlike thymic epithelial cells or peripheral blood lymphocytes, the immunoreactive T alpha 1 (IRT alpha 1) form in the supernatants from tumor cells such as MCF-7 breast carcinoma was of a lower molecular weight than authentic T alpha 1. These studies suggest that the authentic form of T alpha 1 is the major immunoreactive form in normal serum and that it is secreted by the medullary thymic epithelial cells as well as by peripheral blood lymphocytes. An additional immunoreactive form, secreted by tumor cells has also been identified and is the subject of future studies.


In vitro and ex vivo effect of tiaprofenic acid on human peripheral blood mononuclear cells.

The effect of the non-steroidal anti-inflammatory drug (NSAID) tiaprofenic acid on different human immune parameters was investigated in vitro or following in vivo administration in healthy adult volunteers. Results from the in vitro study demonstrated an increased mitogen-induced blastogenesis and interleukin 2 (IL-2) production together with a reduced polyclonal immunoglobulin (Ig) secretion in the presence of the drug. Results from the ex vivo study showed that treatment with tiaprofenic acid had no significant effects on the immune parameters investigated, i.e. unstimulated and mitogen-induced proliferation and IL-2 production, spontaneous and stimulated Ig synthesis, lymphocyte subpopulations, serum Ig and complement levels.


Peptides and their constituent amino acids influence the immune response and phagocytosis in different ways.

To elucidate the role of immunoactive amino acids (which are capable of stimulating the immune response) in the peptide regulation of antibody production and phagocytic processes we have studied the influence of some fragments of natural peptides and the amino acids included in them on the thymus-dependent immune response to sheep red blood cells (SRBC) and on the phagocytosis of Staphylococcus by murine peritoneal neutrophils. It has been found that the effects of amino acids, as well as of peptides that they form, on the immune response and on phagocytosis were diverse. Glutamic and aspartic acids, threonine and valine stimulated both the immune response and phagocytosis. Glycine and isoleucine influenced neither the immune response nor phagocytosis, whereas lysine, proline, tyrosine and leucine did not influence the immune response, but enhanced the phagocytic activity of neutrophils. Arginine inhibited the immune response but stimulated phagocytosis. Peptide TTKD section (the fragment 77-80 of murine Thy-1-antigen) contained in C- and N-terminus amino acids (T and D) which stimulated the antibody production and phagocytosis, and lysine (K) which stimulated phagocytosis only, enhanced both processes. Peptides LGIP and PYIK (the fragments 49-53 and 66-69 of murine Thy-1 antigen) which contained both immunologically inert amino acids (L, G, I, P, Y, K) and phagocytosis stimulating amino acids (L, Y, P, K) influenced neither the immune response nor the phagocytic activity of neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)


Anti-CD3-induced T-cell activation in vivo--I. Flow cytometric analysis of dose-responsive, time-dependent, and cyclosporin A-sensitive parameters of CD4+ and CD8+ cells from the draining lymph nodes of C57Bl/6 mice.

An in vivo model to assess the effects of chemicals on T-cell activation has been characterized and validated using the immunosuppressive drug, cyclosporin A (CsA). The dose response and kinetic effects of the hamster anti-mouse monoclonal antibody 145-2C11 (anti-CD3) on various parameters of T-cell activation were examined in cells from the draining popliteal and inguinal lymph nodes of C57Bl/6 mice. Parameters of anti-CD3-induced T-cell activation included 3H-TdR incorporation (+/- recombinant murine IL-2), and flow cytometric analysis of CD3 and IL-2 receptor (IL-2R) expression on CD4+ and CD8+ cells. Increases in the percentage of lymphocyte subsets in the S/G2M phase of the cell cycle and total cell recovery following anti-CD3 are also reported. Increased 3H-TdR incorporation was maximal over a dose range of 0.25-25 micrograms anti-CD3, while maximal increases in the percentage of CD4+ and CD8+ cycling occurred after a dose of 2.5 micrograms anti-CD3. At 24 h after anti-CD3 treatment, CD3 expression on both CD4+ and CD8+ cells was dose dependently down-modulated while IL-2R expression and IL-2-driven 3H-TdR incorporation were dose dependently increased. In addition, total cell recovery increased at 24 h and correlated with an increase in the percentage of B220+ cells present in the lymph nodes. There was a corresponding decrease in the percentage of Thy 1.2+, CD4+, and CD8+ cells. No increase in cycling of B220+ cells was observed, suggesting an influx of B220+ cells into the node rather than proliferation. Elevation in 3H-TdR incorporation occurred as early as 4 h after anti-CD3 treatment, while increases in the percentage of CD4+ and CD8+ cells cycling were not apparent until 24 h. At 48 h, the percentage of CD8+ cells cycling doubled while the percentage of CD4+ cells cycling remained constant. Down-modulation of CD3 expression on CD4+ and CD8+ cells was apparent as early as 1 h after treatment with less than 10% of CD4+ and CD8+ cells expressing CD3 by 12 h. Induction of IL-2R expression and IL-2-driven 3H-TdR incorporation was maximal at 12 h after anti-CD3. The immunosuppressive drug, CsA (25, 50, or 100 mg/kg, i.p.) decreased anti-CD3-induced 3H-TdR incorporation. Concurrently, anti-CD3-induced increases in the percentage of CD4+ and CD8+ cells cycling were inhibited by CsA. Likewise, IL-2 responsiveness and IL-2R expression on both T-cell subsets were inhibited by CsA.(ABSTRACT TRUNCATED AT 400 WORDS)


Macular oedema and retinal neovascularisation in juvenile diabetics.

Thirteen young diabetic patients with peripheral capillary non perfusion who presented with symptoms of mild maculopathy were reviewed retrospectively. In this group, peripheral retinal ischaemia was often overlooked and a rapidly progressive proliferative retinopathy developed. Fluorescein angiography of the peripheral retina showed capillary closure, but with preservation of arterioles and venules. In this series, half of the eyes lost vision. In seven eyes where the peripheral ischaemia was treated by pan retinal photocoagulation, the maculopathy resolved without any specific laser treatment to the macula. In young diabetics presenting with maculopathy, the peripheral retina should be examined for ischaemia, and if present, pan retinal laser photocoagulation should be performed. Focal treatment for the macular disease can be delayed until after the peripheral photocoagulation, as the maculopathy may remit.


Xerophthalmia clinics in rural eye camps.

Even though the primary prevention of many eye diseases can be effectively incorporated into the existing pattern of rural eye camps, efforts in this direction are restrained and insubstantial. We describe our technique and experience in the prevention of xerophthalmia by organising a distinct entity called a xerophthalmia clinic in our eye camps. The clinic consists of an Ophthalmologist or an Ophthalmic assistant who will exclusively examine children who come to the eye camp. This is perhaps, the first report on rural xerophthalmia clinics, in ophthalmic literature. Over a seven year period from 1984 to 1990 we have conducted 71 xerophthalmia clinics amongst the ninty eye camps organised. A total of 11,370 children were examined in the xerophthalmia clinic out of which 18.9% were afflicted with the disease. Therapeutic doses of Vitamin A were administered on the spot to the afflicted and prophylactic doses were administered to the rest. Intensive health education efforts are made through clinics to effectuate change in dietry habits towards consumption of locally grown DGLV (Dark Green Leafy Vegetables) like Anthenum, chenopodium and Amaranthus. A bipronged offensive consisting of mega-dosing and health education is, for the present and the foreseeable future, the best strategy to combat xerophthalmia in this desert region. A year by year breakdown of prevalence rates in the present study shows that in years of severe drought the prevalence of xerophthalmia increases three fold over the non-drought or mild drought years, thereby demonstrating that drought is a substantial risk factor in developing countries leading to vitamin A deficiency and xerophthalmia.


Anti-retinal S-antigen antibodies in human sera: a comparison of reactivity in ELISA with human or bovine S-antigen.

Various studies have demonstrated anti-retinal S-antigen (S-ag) antibodies in uveitis sera in assays using bovine S-ag. Because of its molecular similarity and cross-reactivity with human S-ag, reactions with bovine S-ag have been considered a reliable indication of anti-S-ag autoimmunity. To test this assumption, the cross-reactivity of purified human and bovine S-ags was quantitated by ELISA titration of various anti-human and anti-bovine S-ag immune reagents raised in mice, rats and rabbits. Anti-human S-ag reagents appeared to be largely cross-reactive with bovine S-ag, whereas anti-bovine S-ag reagents were 6-10 times less reactive with the cross-reacting human S-ag than with bovine S-ag, thus showing a predominant role of species-specific epitopes on bovine S-ag. Furthermore, a large number of human control and uveitis sera was tested in ELISA with both human S-ag- and bovine S-ag-coated microwells. Both the numbers of positive sera and the levels of anti-S-ag antibodies in the two tests significantly correlated, but many exceptions were found, and the predictive value of reactions with bovine S-ag for the presence and levels of anti-S-ag autoantibodies was low. For individual human sera, assessment of anti-S-ag autoantibodies requires the use of human S-ag in immunoassays.


Retinal toxicity of intravitreal lazaroid (21-aminosteroid U75412E).

The 21-aminosteroids or lazaroids are a novel series of compounds being developed for the acute treatment of traumatic or ischemic injury of the nervous system. These compounds were specifically designed to localize within cell membranes and inhibit lipid peroxidation reactions. In this study, 21-aminosteroid U75412E was injected into the vitreous body of rabbit eyes to evaluate its suitability for intraocular injection and its toxicity on intraocular tissues. Doses ranged from 20 micrograms to 200 micrograms. Retinal toxicity was determined through light and transmission electron microscopy and electroretinography. No retinal toxicity was noted in doses of 30 micrograms and below.


Ocular involvement in acute lymphoblastic leukemia: an echographic study.

We report a case of acute lymphoblastic leukemia (ALL) with ocular involvement in which bilateral swelling of the optic disk head was noticed. Massive direct infiltration of the optic nerve head by leukemic cells can give rise to a clinical picture identical to that of a true papilledema. Ocular echography allowed a better and more complete interpretation of the optic disk involvement. No echographic description of a leukemic infiltration of the optic nerve head has been reported previously.


Postural behaviour of intraocular pressure following trabeculoplasty.

Postural behaviour of intraocular pressure (IOP) was studied in 29 glaucomatous eyes before and after argon laser trabeculoplasty (ALT) and compared with that of 60 normal eyes. Although argon laser trabeculoplasty was successful in lowering the IOP below 21 mm Hg, it produced little effect on the postural behaviour of the IOP. No significant change was observed in the amplitude of postural rise of IOP in ALT treated eyes.


Biophysical characteristics of the Meibomian lipid layer under in vitro conditions.

The biophysical behaviour of the Meibomian gland secretion was tested under in vitro conditions. Thereby, simultaneous recording of surface pressure and surface potential was performed. The Meibomian lipid layer was compared with other surface-active components like polyvinylalcohol and polyvinylpyrrolidone. On the other hand, Eledoisin was tested as an example for a surface-inactive substance. An attempt was made to describe the biophysical interaction between a given artificial tear substitute and the Meibomian lipid layer. With respect to the surface potential Dipalmitoyl-phosphatidyl-choline was established as an analogue for Meibomian gland secretion. Fluorescence measurements in the presence of a cyanine dye (1 N,N'dioctadecyloxacarbocyanine) were used as a method to localize the site of the characteristic potential change. From the fluorescence spectra under compression we conclude that the molecular change takes place at the lipid-subphase interface of the Meibomian lipid layer.


Astigmatism following cataract surgery: comparison of a scleral and a corneal incision in a mixed group of patients with and without glaucoma.

We retrospectively analysed the course of postoperative corneal astigmatism and corrected visual acuity after extracapsular cataract extraction and posterior chamber lens implantation with either a corneal or a scleral incision in 170 eyes of 155 patients with and without glaucoma. A continuous 10/0 nylon shoelace suture was used for wound closure in two groups. In a third group, corneal wound closure was performed with a shorter shoelace suture in combination with two vicryl wing sutures at 11 and 1 o'clock. Although early postoperative mean astigmatism in eyes operated through a corneal incision was high (range 2.92-6.67 diopters at 1 month postoperatively) and significantly different when compared to eyes operated through a scleral incision (1.96 diopters), final mean astigmatism did not differ significantly between those two groups. Moreover, in 27% of eyes operated through a corneal incision, mean astigmatism at 2 months postoperatively was not significantly different from the scleral group and suture removal was not necessary. There was no statistically significant difference in corrected visual acuity over the entire study period between groups. Since safety and functional results of the corneal incision were not different from the scleral incision, we prefer a corneal incision in cataract surgery because of its surgical advantages, especially in patients with cataract and coexisting glaucoma.


Berson test for blue cone monochromatism.

The Berson test for blue cone monochromatism discriminates X-linked blue cone monochromatism from achromatopsia but not from X-linked progressive c dystrophy.


Anterior segment photography using the Oxford retro-illumination camera.

The use of the Oxford retro-illumination camera in documenting cataract is now well established. Repeatability has been shown to be good. This article describes its use in photographing the anterior segment of the eye.


Transcription and replication of animal mitochondrial DNAs.

The development of in vitro transcription and replication systems has allowed the identification of promoter sequences and origins of replication for several animal mtDNAs. As a consequence, the necessary reagents and basic information are available to permit the characterization of transacting factors that are required for transcription and replication. All of the animal trans-acting species purified at this time are known or reasoned to be nuclear gene products. There is now the opportunity to learn how these nuclear genes are regulated and the mechanisms that are utilized for the import of their products into the organelle. With regard to import, the human transcription factor mtTF1 appears to have an amino-terminal sequence characteristic of other imported mitochondrial proteins (Parisi and Clayton, 1991). An interesting issue is the degree to which fundamental features of mtDNA replication and transcription are conserved between species. With regard to animal mtDNAs, there is very little in the way of conservation of DNA sequence at the promoters and origins of replication. The exceptions to this are the presence of a characteristic stem-loop L-strand origin of replication sequence in vertebrates [except for chicken mtDNA (Desjardins and Morais, 1990)] and the general presence of CSBs II and III (and to a lesser extent CSB I) in most higher animal mtDNAs. Because mtDNA promoters are not highly conserved, it is perhaps not surprising that general cross-species transcription does not occur, except for very limited examples of closely related species and sequences (Chang et al., 1985b). Using crude mtRNA polymerase holoenzyme preparations, there is no specific transcriptional initiation when proteins from human mitochondria are used with mouse mtDNA promoter templates, and vice versa. However, in contrast to this overall observation, purified fractions of human or mouse mtTF1 can be exchanged and shown to function across species boundaries (Fisher et al., 1989). The ability of mitochondrial mtTF1-type proteins to operate across even greater evolutionary distances was suggested by the ability of human and yeast proteins to recognize some mitochondrial promoter sequences in common (Fisher et al., 1992). More recent studies suggest that human mtTF1 can substitute for its yeast homolog in vivo, and thereby perform at least the most critical functions required to maintain yeast mtDNA in the cell (M.A. Parisi, B. Xu, and D.A. Clayton, submitted for publication). The other sites of conserved macromolecular interactions are related to the two origins of DNA replication.(ABSTRACT TRUNCATED AT 400 WORDS)


A review of the nature and activity of a general surgical service in Ireland.

The steady increase in hospital costs has led to demands for closer scrutiny of activity levels, workloads and outcomes. This study sought to examine these parameters in a typical district general surgical unit in this country. In the five year period 1985-89, 11,227 inpatient and 3,354 outpatient procedures were performed; 83% of the inpatient procedures were elective and 17% were emergency surgical operations. All inpatient procedures were categorized: minor (41%), intermediate (42%) and major (17%). A prospective one year review in 1990/1991 confirmed the accuracy of the retrospective data. During that year 2,335 inpatient operations and 765 outpatient operations were performed, of which 80.5% of the inpatient operations were elective and 19.5% were emergency procedures. Of these 16.6% were major, 34.4% intermediate and 49% were minor operations. 60% of the operations were performed by consultants. The in-hospital surgical mortality for the 1 year prospective review was 1.35% and the perioperative mortality was 0.64%. The overall operation morbidity rate was 9% and the procedure-related morbidity was 4.7%. The wound infection rate was 2%. Of the common operations performed throughout the six year study period appendicectomies and external hernia operations accounted for 20% of the caseload; 14% were urological, 7% were breast and 6% were biliary operations. The average waiting time for elective admissions was less than 4 weeks. The average length of hospital stay and the bed occupancy rates did not change.


Contemporary risk factors for sudden infant death in an Irish population--a case control study.

This case-controlled study examines some recently implicated risk factors for Sudden Infant Death Syndrome (S.I.D.S.) in Irish infants. Irish S.I.D.S. infants are lighter at birth than controls (3463g) compared to (3542g) and boys out-number girls by a ratio of 1.3:1. S.I.D.S. infants are more frequently: breast-fed (42% vs 25%) and sleep in a location other than the parent's bedroom (54% vs 21%), but start solids at a similar age and appear not to be sicker prior to death than the control group. This study highlights the frequency of symptoms of possible ill-health (i.e. snuffles and being "chesty") in well infants during the first months of life with 32% of the control group having snuffles and 35% described as "chesty". In addition these symptoms are frequently treated with antibiotics with 31% of the control group having already received antibiotics by 2 months of age. A majority of S.I.D.S. infants were described as cold when found (52%) with 39% described as warm and 15% as sweaty. Obviously the recently implicated role of overheating may be relevant in the latter 15% of S.I.D.S. cases. In this series, 88% of infants had died by 6 months of age. Of the 97 parents of S.I.D.S. infants questioned, 78 had subsequently become pregnant by the time the study was conducted at an average time of 5 months post the S.I.D.S. event.


The correlation between clinical diagnosis of knee pathology and findings at arthroscopy.

175 patients referred for arthroscopy were studied prospectively to assess the accuracy of clinical examination supplemented by standard radiology in the evaluation of knee symptoms. Clinical diagnosis of medial meniscal tears was inaccurate while greater confidence could be placed in the diagnosis of anterior cruciate ligament and lateral meniscus tears. Clinical accuracy rates could be improved if patients with minimal symptoms were excluded from arthroscopy examination.


Hyperthyroidism associated with acute suppurative thyroiditis.

Acute suppurative thyroiditis is a rare condition with potentially serious complications. It has been suggested that hyperthyroidism may be a feature in occasional cases but this has been poorly documented. We describe a patient in whom acute suppurative thyroiditis caused transient hyperthyroidism.


Colo-rectal carcinoma 1975 and 1990: no improvement in the stage of disease at resection.

There is no overall consensus as to what screening patterns should be adopted for individuals of average risk for colo-rectal carcinoma. The single most important prognostic factor in survival is the stage of the colo-rectal neoplasm at the time of resection. Consequently significant resources have been directed to early detection while the disease is at a curative stage. To assess the impact of widespread availability of faecal occult blood testing and large bowel endoscopy we prospectively examined all large intestine specimens resected for carcinoma in 1990 and compared them with specimens resected for colonic carcinoma in 1975. We excluded adenomatous polyps with malignant change which had been treated by snaring at colonoscopy, without subsequent colectomy, as their precise Duke's staging was so difficult. In any event, their numbers were small (> 5 in 1990). Our study shows that despite the resources targeted at early diagnosis of colo-rectal carcinoma resection of tumours at a prognostically favourable stage has not been improved in the 25 years since 1975.


The role of designated driver programs in the prevention of alcohol-impaired driving: a critical reassessment.

We review the "designated driver" concept and the current debate over its role in preventing alcohol-impaired driving. In our view, the focus on this strategy by broadcasters, the alcohol industry, and various public service groups has deflected attention from other alcohol-related problems that account for the vast majority of deaths and injuries associated with alcohol use. This focus has also distracted many public health advocates and policymakers from the bigger and more important jobs of increasing public awareness of the social, environmental, and economic factors that influence alcohol consumption and promoting debate on legislation and other public policy solutions to alcohol-impaired driving. As part of a comprehensive strategy, we strongly encourage a renewed focus on "sobriety checkpoints," strict enforcement of laws against alcohol sales to minors, alcohol advertising reform, increased excise taxes, and other public policy initiatives supported by the Surgeon General. These measures will curb underage and heavy alcohol consumption and will create a legal and social environment in which individuals are motivated to avoid impaired driving through several alternative strategies, including but not limited to the use of designated drivers.


Mammography usage and the health belief model.

Regular screening mammograms for asymptomatic women are the most effective method for early detection of breast cancer. This study assessed the relative influence of Health Belief Model (HBM) constructs on prior mammography usage and the intention to obtain mammograms with data from a sample of 1,057 women over the age of 35 years residing in an urban community in the United States. Covariance structure analysis with latent variables was used initially to perform a confirmatory factor analysis of indicators of Socioeconomic Status (SES), Perceived Susceptibility, Perceived Barriers, Perceived Benefits, Cues to Action, Prior Mammography, and Future Intentions. Once a plausible factor structure was confirmed, a predictive path model was tested with Future Intentions and Prior Mammography as the outcome variables. Cues to Action, operationalized as a physician influence variable, particularly impacted Prior Mammography, and Perceived Susceptibility was the most powerful predictor of Future Intentions. SES only related significantly to Perceived Barriers, and Cues to Action, and did not directly influence Prior Mammography and Future Intentions. HBM predictor variables alone accounted for the relationship between previous mammography experience and intentions to obtain mammograms in the future. Health education implications and an applied outreach program are discussed.