Degenerative myelopathy in two Boxer dogs.

Degenerative myelopathy (DM) is a common, slowly progressive, debilitating disease reported in several dog breeds, including the German Shepherd Dog and Pembroke Welsh Corgi. Boxer dogs present occasionally for a thoracolumbar myelopathy for which no cause is identified on MRI or cerebrospinal fluid analysis. Despite a lack of a histologic description of DM in the Boxer in the veterinary literature, such dogs are presumed to have DM. Here we report 2 histologically confirmed cases of DM in the Boxer breed in which histologic studies disclosed marked degenerative changes in the spinal cord that were most prominent in the thoracic and cranial lumbar segments. Lesions consisted of myelin vacuolation and degeneration, myelophagocytosis, reactive astrocytosis, and ellipsoid formation most prominent in the lateral and ventral funiculi. We present a detailed histologic description of DM in the Boxer dog and compare it to DM in other purebred dogs.

inlA premature stop codons are common among Listeria monocytogenes isolates from foods and yield virulence-attenuated strains that confer protection against fully virulent strains.

Previous studies showed that a considerable proportion of Listeria monocytogenes isolates obtained from foods carry a premature stop codon (PMSC) mutation in inlA that leads to production of a truncated and secreted InlA. To further elucidate the role these mutations play in virulence of L. monocytogenes, we created isogenic mutants, including (i) natural isolates where an inlA PMSC was reverted to a wild-type inlA allele (without a PMSC) and (ii) natural isolates where a PMSC mutation was introduced into a wild-type inlA allele; isogenic mutant sets were constructed to represent two distinct inlA PMSC mutations. Phenotypical and transcriptional analysis data showed that inlA PMSC mutations do not have a polar effect on the downstream inlB. Isogenic and natural strains carrying an inlA PMSC showed significantly reduced invasion efficiencies in Caco-2 and HepG2 cell lines as well as reduced virulence in oral guinea pig infections. Guinea pigs were also orally infected with a natural strain carrying the most common inlA PMSC mutation (vaccinated group), followed by challenge with a fully virulent L. monocytogenes strain 15 days postvaccination to probe potentially immunizing effects of exposure to L. monocytogenes with inlA PMSC mutations. Vaccinated guinea pigs showed reduced bacterial loads in internal organs and improved weight gain postchallenge, indicating reduced severity of infections in guinea pigs exposed to natural strains with inlA PMSC mutations. Our data support that (i) inlA PMSC mutations are causally associated with attenuated virulence in mammalian hosts and (ii) naturally occurring virulence-attenuated L. monocytogenes strains commonly found in food confer protective immunity.

'People like me don't make things like that': Participatory video as a method for reducing leprosy-related stigma.

The Stigma Assessment and Reduction of Impact project aims to assess the effectiveness of stigma-reduction interventions in the field of leprosy. Participatory video seemed to be a promising approach to reducing stigma among stigmatized individuals (in this study the video makers) and the stigmatisers (video audience). This study focuses on the video makers and seeks to assess the impact on them of making a participatory video and to increase understanding of how to deal with foreseeable difficulties. Participants were selected on the basis of criteria and in collaboration with the community health centre. This study draws on six qualitative methods including interviews with the video makers and participant observation. Triangulation was used to increase the validity of the findings. Two videos were produced. The impact on participants ranged from having a good time to a greater sense of togetherness, increased self-esteem, individual agency and willingness to take action in the community. Concealment of leprosy is a persistent challenge, and physical limitations and group dynamics are also areas that require attention. Provided these three areas are properly taken into account, participatory video has the potential to address stigma at least at three levels - intrapersonal, interpersonal and community - and possibly more.

Nucleotide sequence and genetic organization of the genome of the N-specific filamentous bacteriophage IKe. Comparison with the genome of the F-specific filamentous phages M13, fd and f1.

The nucleotide sequence and genetic organization of the genome of the N-specific filamentous single-stranded DNA phage IKe has been established and compared with that of the F-specific filamentous phages M13, fd and f1 (Ff). The IKe DNA sequence comprises 6883 nucleotides, which is 476 (475) nucleotides more than the nucleotide sequence of the Ff genome. The data indicate that IKe and Ff have evolved from a common ancestor (overall homology approx. 55%) and that their genomes contain ten homologous genes, the order of which is identical. Similar to Ff, the major coat protein and the gene III-encoded pilot protein of IKe are synthesized via precursor molecules. The extent of homology between the genes of IKe and Ff differs significantly from one gene to another. Genes that code for viral capsid proteins are less homologous than genes whose products are involved in the processes of DNA replication and phage morphogenesis. During evolution, large nucleotide sequence rearrangements have occurred in the gene (gene III) whose product is needed for the attachment of the virion to the conjugative pili of the host cell, suggesting that these rearrangements have led to phages with different host specificities. Extensive nucleotide sequence homology was noted between the structural elements involved in DNA replication and phage morphogenesis, indicating that the mechanisms involved in DNA replication and morphogenesis are highly conserved.

Nonsurgical treatment of splenic hemorrhage in an adult with infectious mononucleosis. Case report and review.

A case is presented of a young adult with splenic hemorrhage secondary to infectious mononucleosis. The patient was managed successfully without surgery and has done well over the long term with progressive resolution of the hematoma on ultrasound. The implications of this case for the management of patients with this syndrome are discussed.

Fuzzy cluster analysis of positive stress tests, a new method of combining exercise test variables to predict extent of coronary artery disease.

Fuzzy set theory is useful in the analysis of data having a graded degree of abnormality. Previous studies using sharp cutoff points between normality and abnormality have resulted in general guidelines for the interpretation of positive stress tests, but do not enable the clinician to simultaneously combine several stress test variables, each having a range of abnormality. In this study, positive stress test results from 109 patients were reviewed. An angiogram recorded within 1 month of the stress tests showed that 100 patients had coronary artery disease (CAD) (15 had left main CAD, and 27 had 3-vessel, 30 had 2-vessel, and 28 had 1-vessel disease) and 9 were normal. Six variables were selected for fuzzy cluster analysis: ST-segment change, difference between resting systolic and peak exercise systolic blood pressure, total treadmill time, peak exercise heart rate as a percentage of 100% predicted maximum for age, time to onset of angina, and duration of repolarization abnormalities. The analysis used a similarity measure to compute how closely each stress test resembled a prototypical mildly, moderately, or severely abnormal stress test. Stress tests classified by this method showed better correlation with the extent of CAD than the degree of ST-segment depression alone. Unlike tests with mild degrees of ST depression (0.5 to 1.5 mm), tests classified as mild by the method virtually excluded high-grade CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

A nomogram for planning respiratory therapy.

A nomogram is presented which aids in monitoring and selecting therapy in the treatment of the patient with hypoxemia. It facilitates accurate bedside determination of total shunt fraction and estimation of the arterial oxygen tension (PaO2) attainable at inspired oxygen concentrations of 21 percent to 100 percent. The nomogram permits rapid consideration of changes in hemoglobin concentration, arteriovenous oxygen content difference, and shunt fraction on the PaO2. The uses of the nomogram in several therapeutic contexts are discussed.

Epidural anesthesia following thoracotomy in patients with chronic obstructive airway disease.

Epidural analgesia for control of postoperative thoracotomy pain in patients with carcinoma of the lung and chronic obstructive airway disease is described. The rationale and procedure for its use are presented. Epidural analgesia used in 8 patients requiring pulmonary resection who had chronic obstructive airway disease resulted in an improved postoperative course and avoided use of narcotics or a respirator in 7 of the 8 patients.

A simplified method to determine functional residual capacity during mechanical ventilation.

We describe a nonrecirculating helium-rebreathing method providing rapid and simple measurement of the functional residual capacity (FRC) in spontaneously breathing subjects and patients receiving mechanical ventilation. Results of triplicate determinations in 24 normal subjects revealed a repeatability of +/- 5.2 percent of the measured FRC, results similar to those predicted for these subjects. Results in six additional subjects were not significantly different from those obtained with a standard method using helium equilibration in the pulmonary function laboratory. Triplicate determinations in eight patients after cardiac surgery demonstrated similar repeatability. In 22 other patients studied after open-heart surgery, the FRC fell more in those who could not be weaned than in those who could be weaned from the respirator. Since an increase in FRC is the goal of therapy with positive end-expiratory pressure, this method should be useful in determining the efficacy of a particular level of positive end-expiratory pressure.

Mechanical work on the lungs and work of breathing with positive end-expiratory pressure and continuous positive airway pressure.

The mechanical work on the lung required during spontaneous breathing with positive end-expiratory pressure (PEEP) was compared with different methods of continuous positive airway pressure (CPAP) in nine young healthy athletes (surfers) at levels of 5, 10, 15, and 20 cm H2O. At the level of 20 cm H2O, PEEP increased the mean total work per minute by 116 percent and the total work per liter by 121 percent. The percent increase rose linearly with the level of PEEP. In contrast, with methods of CPAP that maintained the airway pressure (Paw) constant, the total work per minute decreased by 45 per cent at a PEEP of 10 cm H2O and remained at this level with PEEP of 15 and 20 cm H2O. Use of PEEP did not increase the functional residual capacity (FRC) in these spontaneously breathing subjects. In contrast, CPAP resulted in a rise in FRC proportional to the level of CPAP. This suggests that CPAP must be applied in a manner that maintains Paw constant to provide optimal assistance to ventilation.

The effects of carbon dioxide on pulmonary mechanics in hyperventilating, normal volunteers.

Transpulmonary pressure, air flow, and end-tidal carbon dioxide levels were measured in normal human volunteers during hypocapnic, eucapnic, and hypercapnic hyperventilation. Respiratory rate and tidal volumes were well matched at a minute ventilation of 52 L. on three inspired gas mixtures: 21 per cent oxygen and 79 per cent nitrogen; 5 per cent carbon dioxide, 21 per cent oxygen and 74 per cent nitrogen; and 12 per cent carbon dioxide, 21 per cent oxygen and 67 per cent nitrogen. Respiratory rate, tidal volume, lung compliance, resistance, and resistive work per liter were calculated with a digital computer. In 13 experiments in 7 normal volunteers, no net bronchoconstriction or bronchodilatation was observed when eucapnic hyperventilation was compared to hypocapnic or hypercapnic hyperventilation. During hyperventilation of this degree, a change in bronchomotor tone owing to alteration in arterial or alveolar PCO2 either does not occur or else is masked by other reflexes or mechanical factors acting on the bronchi.

Predicting the need for prolonged ventilatory support in adult cardiac patients.

Forty-nine cardiac surgical patients had ventilatory function tests and measurements of maximum inspiratory (MIP) and maximum expiratory (MEP) pressures preoperatively. The differences between the values of various function tests were compared for patients requiring less than 24 hours of ventilator support and those requiring more than 24 hours. There was a significant difference in the mean values for the two groups in vital capacity (VC) first-second forced expired volume (FEV) midexpiratory flow between 50 and 75 (MMEF 50--75) and 75--85 percent of expired volume (MMEF 75--85), and MEP. The standard deviations of each of the variables were so large that the clinical usefulness was limited. However, when discriminant analysis was used for more than one variable, the combination of MMEF 75--85 and MEP predicted success or failure to wean in 24 hours correctly in 90 percent of instances. On the basis of these simple tests, patients predicted to succeed should be weaned from ventilator support on recovery from anesthesia. Those predicted to fail should be placed on intermittent mandatory ventilation (IMV) and should be weaned following a planned, logical process.

Postpneumonectomy pulmonary edema.

Postpneumonectomy pulmonary edema has become a worldwide problem. Study of data available from some of these patients implicates excessive perioperative volumes of intravenous fluid. A study done on dogs supports the clinical conclusion. The risk factors for this complication are right pneumonectomy, large perioperative fluid load, and high intraoperative and postoperative urine outputs. Patients undergoing pneumonectomy are at greater risk from intravenous fluid therapy than other types of patients.

The effect of pH on the hypothermic ventricular fibrillation threshold.

During cardiac operations using hypothermia, the pH measured at 37 degrees C (and corrected to the patient's body temperature) is generally kept at 7.40. However, ectotherms (cold-blooded animals) regulate pH alkaline of 7.40 as temperature falls, e.g., pH 7.58 at 25 degrees C. Hypothermia and acidosis increase the propensity for ventricular fibrillation (VF). This study was undertaken to determine which scheme of pH regulation during hypothermia provided the highest level of cardiac electrical stability. Eleven dogs underwent median sternotomy and implantation of right ventricular and limb electrodes, aortic and central venous pressure catheters, and a probe to measure pulmonary artery blood temperature. To determine the VF threshold, a programmable stimulator was used to find the minimum current needed to produce VF by sweeping the vulnerable period of the cardiac cycle. The animals were divided into two groups for pH management: eight in the clinical scheme (pH 7.4) and seven in the ectothermic scheme, where pH varied with temperature. Control values were recorded prior to cooling and then repeated when core cooling had lowered the temperature to 25 degrees C. In the clinical group, the VF threshold decreased from 23.1 +/- 4.1 mA at 37 degrees C to 17.0 +/- 3.4 mA at 25 degrees C (p = 0.002); in the ectothermic group, the VF threshold was unchanged by hypothermia (23.7 +/- 3.2 to 22.8 +/- 2.8 mA). Heart rate and arterial and central venous pressures were not different between the groups at either temperature. Corrected arterial pH and PCO2 were unchanged from control in the clinical group at 25 degrees C (pH 7.40 +/- 0.01, arterial PCO2 34 +/- 2 torr), whereas arterial PCO2 was maintained at 20 +/- 1 torr to achieve pH 7.59 +/- 0.01 in the ectothermic group. Five of the eight dogs in the clinical group had spontaneous VF while cooling, as compared to one of the seven dogs in the ectothermic group. These studies demonstrate that allowing the corrected pH to rise with hypothermia and remain alkalotic relative to pH 7.4 improves the electrical stability of the heart during hypothermia, as evidenced by the VF threshold at 25 degrees C. Since the ectothermic scheme increases the electrical stability of the heart, it could decrease the incidence of VF during hypothermia and decrease the temperature at which VF occurs during hypothermic cardiopulmonary bypass.

Selective use of ventilator therapy in flail chest injury.

We have prospectively treated 36 patients with flail chest using a treatment protocol for limited use of mechanical ventilation. Age of the patients ranged from 6 months to 83 years. Patients were divided into three groups dependent upon their clinical presentation and need for respiratory support: Group I patients had severe pulmonary dysfunction-tachypnea, dyspnea, arterial PO2 less than or equal to 60 torr, arterial PCO2 greater than or equal to 50 torr or shunt fraction greater than or equal to 25%. Group II patients had no pulmonary dysfunction but did require temporary respirator support for an associated injury. Group III patients had no pulmonary dysfunction. Thirteen patients were assigned to Group I. They required respiratory support for an average of 10.5 days; 11 of the 13 had complications, and there were two deaths in this group resulting from a combination of respiratory failure and myocardial infarction. Seven patients were assigned to Group II. six patients were extubated immediately postoperatively; one patient with a head injury was hyperventilated for 48 hours to reduce intracranial pressure and then extubated. Sixteen patients were assigned to Group III. Fifteen required no ventilatory support. One 83-year-old man developed pneumonia and was mechanically ventilated for 31 days. Early effective pain control and chest physiotherapy were critical to success and were used in all patients. Increase in respiratory rate, fall in tidal volume or vital capacity, and increased pain were used as criteria for administration of analgesia. Nonventilatory therapy of flail chest reduces morbidity, mortality, and hospital cost.

Multiorgan scans for staging lung cancer. Correlation with clinical evaluation.

One hundred consecutive patients with findings suggestive of resectable bronchogenic carcinoma were studied prospectively to determine if routine liver, brain, and bone scans (multiorgan scans) detected metastases which were not suggested by a history, physical examination, and serum chemistries. Multiorgan scans were compared with clinical evaluations in 52 patients found to have operable bronchogenic carcinoma. There was a discordance between scans and clinical evaluations in 25/153 scans (16 per cent). Two of the 22 negative scans in patients with abnormal clinical findings were false negative. Sixteen of the 17 positive scans in patients with normal clinical findings were false positive. One of the 131 scans done in patients with no evidence of metastases on clinical evaluation was true positive. These data indicate that the routine use of multiorgan scans in the initial staging of potentially resectable bronchogenic carcinoma is not justified.

Interstitial hydrostatic pressures in patients undergoing CABG and valve replacement.

Using the Scholander-Hargens wick technique to measure interstitial fluid hydrostatic pressure (IFP) in thigh muscle (MIP) and subcutaneous tissue (SQIP), we have studied 12 patients undergoing cardiopulmonary bypass (CPB). Simultaneous measurements were made of serum total proteins (TP) and colloid osmotic pressure (COP). Bypass was carried out with a nonblood, noncolloid prime. In the postoperative period, colloid and blood were given which raised COP above prebypass levels (see Table II). MIP rises more with hemodilution than does SQIP and is less negative throughout. MIP rises faster when COP drops than does SQIP. These findings suggest that subcutaneous tissue interstitial space is loose and has a high compliance, whereas muscular tissue interstitial space is tight and has a low compliance. The increased pressure represents increase in fluid which is then removed promptly as COP is restored in the postoperative period. Experimental studies in animals show a response similar to MIP in the myocardium.

Measuring lung volumes from chest films using equations derived from computed tomography.

Computed tomographic scans show true cross-sectional area of a segment of the chest. Measurement of the cross-sectional area of the lung at several adjacent levels permits calculation of a geometrically defined volume. CT scans from 26 cases were used to derive equations to predict regional volume from measurements which can be obtained from plain PA and lateral chest films. Separate equations were derived for slices above and below the top of the diaphragm. The best correlation between linear dimensions and true volume was obtained with equations that used lung width and antero-posterior (AP) diameter of each scan, maximum AP lung diameter, and relative scan level (apex to base). These equations predicted the volumes of individual slices above the diaphragm with a correlation coefficient (r) of 0.99 on the right, 0.97 on the left. Below top of the diaphragm, r was 0.91 on the right, 0.92 on the left. Total lung volume was predicted with an r of 0.98 (s.e. 4.8%) on the right and 0.97 (s.e. 5.3%) on the left. Using total chest width instead of AP diameter of each slice reduced r to 0.96 for the volume of either lung. This method compares favorably with previous regression or geometric approximation methods for total lung volume and also makes it possible to obtain estimates of portions of lung volume from chest films.

Hypertonic sodium lactate versus lactated ringer's solution for intravenous fluid therapy in operations on the abdominal aorta.

Fifty-eight patients who were to undergo aortic reconstruction were prospectively randomized into two groups to compare the effects of perioperative fluid replacement with isotonic and hypertonic crystalloid solutions. Blood loss was replaced with packed red blood cells, and additional fluid was given as either Ringer's lactate solution (RL, 130 mEq sodium/L, 274 mOsm/L) or a hypertonic balanced salt solution (HSL, 250 mEq sodium/L, 514 mOsm/L). Fluid was administered to maintain the cardiac filling pressure within 3 torr of the preoperative level and the cardiac output (CO) at or above the preoperative level. The groups were similar with respect to age, preexisting disease, duration of operation, and operative blood loss. During the operation, the RL group required 9.5 +/- 0.8 L of fluid, whereas the HSL group required 4.5 +/- 0.3 L (P less than 0.001). Pulmonary, cardiac, and renal functions were adequately maintained in both groups. There were no significant differences between the groups with regard to CO, urine output, or creatinine clearance during the operation and early postoperative period. Postoperatively, the intrapulmonary shunt was 20 +/- 1% in the RL group and it was 16 +/- 1% in the HSL group (P less than 0.05). The amount of sodium infused and the cumulative sodium balance at the completion of the study period were similar in both groups. Serum sodium and osmolarity were significantly greater in the HSL group (P less than 0.001), reaching a maximum of 151 +/- 1 mEq/L and 305 +/- 2 mOsm/L, respectively. Two patients in the HSL group had a persistent elevation in serum osmolarity (greater than 320 mOsm/L) during operation, for which they received RL for the balance of the resuscitation. There were no complications that could be attributed to the hypertonicity of the solution. HSL is effective for resuscitation of patients with extracellular fluid deficit and is safe provided that the serum sodium and osmolarity are monitored during periods of large volume administration.

Crystalloid vs. colloid resuscitation: is one better? A randomized clinical study.

The effects of hemodynamic resuscitation with protein-containing or balanced salt solution were studied prospectively in 29 patients undergoing abdominal aortic surgery. Blood loss was replaced with packed red cells and extracellular volume with either Ringer's Lactate (RL) or 5% albumin in Ringer's lactate (ALB). Fluids were given to maintain the pulmonary capillary wedge pressure (PCWP) equal to or within 5 torr above preoperative (PO) levels, the cardiac output (CO) equal to or greater than preoperative values, and the urine output at least 50 ml/hr. Serum colloid osmotic pressure (COP), CO, PCWP, the gradient between COP and PCWP (COP-PCWP), and intrapulmonary shunt (Qs/Qt) were measured PO, intraoperatively (IO), and daily for 3 days. The measured variables were similar PO in both groups. Operation time, estimated blood loss, and transfusions were similar. Total fluids received for resuscitation (day of operation) was 11.3 +/- 0.8 liters (RL) and 6.2 +/- 0.4 liters (ALB). Fluid balance at the end of resuscitation was 8.4 +/- 0.8 liters (RL) and 3.4 +/- 0.5 liters (ALB). Maximum decrease in COP was 40% (P less than 0.001) in the RL group and was insignificant in the ALB group. The COP-PCWP decreased from 11 +/- 1 to 2 +/- 1 in RL (P less than 0.001) and insignificantly in ALB. Qs/Qt increased slightly in both groups following operation but was not different between groups. Fluid balance, total fluid infused, sodium balance, total sodium infused, COP, or COP-PCWP did not significantly correlate with Qs/Qt. Two patients in the ALB group experienced pulmonary edema associated with normal COPs and elevated PCWPs. There were no cases of pulmonary edema associated with low COPs and normal PCWPs in the crystalloid group. These data seriously question the necessity to maintain COP by using protein-containing solutions during acute hemodynamic resuscitation. When titrated to physiological end points, even large volumes of balanced salt solutions are tolerated well.