Gastrointestinal cytomegalovirus infection in heart and heart-lung transplant recipients.

Cytomegalovirus (CMV) causes major morbidity in organ transplant recipients. Gastrointestinal disease was the most prominent manifestation of CMV infection in a population of heart and heart-lung transplant patients, with an incidence of 9.9%, compared with pneumonitis (4.0%) and retinitis (0%), and occurred most frequently in CMV-seronegative recipients of organs from CMV-seropositive donors. Clinical manifestations included gastritis (nine patients), gastric ulceration (four patients), duodenitis (three patients), esophagitis (one patient), pyloric perforation (one patient), and colonic hemorrhage (one patient). Patients with gastrointestinal CMV infection were treated with intravenous ganciclovir sodium therapy, 5 mg/kg twice daily, for 2 to 8 weeks, with positive clinical, endoscopic, histologic, and virologic responses. Relapses occurred in four of nine patients who were followed up for a median period of 18 months. Retreatment resulted in healing of endoscopic lesions and in viral clearing. We conclude that early endoscopic evaluation for CMV is indicated in heart and heart-lung transplant patients with gastrointestinal symptoms. This study further suggests that intravenous ganciclovir therapy is effective for the treatment of gastrointestinal CMV in these patients.

Epstein-Barr virus-associated myelopathy in an adult.

A 55-year-old man had a myelopathic syndrome and serologic evidence of Epstein-Barr virus infection. The patient's age and the neurologic and serologic findings suggested reactivation of a latent virus with direct invasion of the CNS. Epstein-Barr virus may exist in a latent state within the nervous system, and should be considered in myelopathic syndromes, even in older patients.

Unusual acute neurologic presentations with Epstein-Barr virus infection.

We describe two patients with serologic evidence of active Epstein-Barr virus infection who presented with unusual neurologic manifestations and minimal systemic findings of infectious mononucleosis. One girl developed an acute hemiplegic migraine syndrome followed by acute psychosis, and the other patient had severe, generalized chorea. The wide spectrum of presenting central nervous system findings associated with Epstein-Barr virus infections underscores the need to suspect this agent in a variety of acute neurologic syndromes.

Welding-related parkinsonism: clinical features, treatment, and pathophysiology.

OBJECTIVE: To determine whether welding-related parkinsonism differs from idiopathic PD. BACKGROUND: Welding is considered a cause of parkinsonism, but little information is available about the clinical features exhibited by patients or whether this is a distinct disorder. METHODS: The authors performed a case-control study that compared the clinical features of 15 career welders, who were ascertained through an academic movement disorders center and compared to two control groups with idiopathic PD. One control group was ascertained sequentially to compare the frequency of clinical features, and the second control group was sex- and age-matched to compare the frequency of motor fluctuations. RESULTS: Welders were exposed to a mean of 47,144 welding hours. Welders had a younger age at onset (46 years) of PD compared with sequentially ascertained controls (63 years; p < 0.0001). There was no difference in frequency of tremor, bradykinesia, rigidity, asymmetric onset, postural instability, family history, clinical depression, dementia, or drug-induced psychosis between the welders and the two control groups. All treated welders responded to levodopa. Motor fluctuations and dyskinesias occurred at a similar frequency in welders and the two control groups. PET with 6-[18F]fluorodopa obtained in two of the welders showed findings typical of idiopathic PD, with greatest loss in posterior putamen. CONCLUSIONS: Parkinsonism in welders is distinguished clinically only by age at onset, suggesting welding may be a risk factor for PD. These preliminary data cannot exclude a genetic contribution to susceptibility in these exposed individuals.

Diminished regional cerebral blood flow response to vibration in patients with blepharospasm.

OBJECTIVE: To determine whether patients with blepharospasm have abnormal sensorimotor processing similar to patients with writer's cramp. BACKGROUND: Blepharospasm is a focal dystonia manifest by involuntary, excessive blinking and squeezing of the eyes. Altered sensorimotor processing may contribute to the development of dystonic movements. Previously the authors demonstrated decreased vibration-induced cortical blood flow responses in hand primary sensorimotor area (PSA) in patients with hand dystonia. METHODS: In this prospective, case-control study, seven patients with blepharospasm were compared with seven normal subjects. PET measurements of regional blood flow were obtained using bolus administration of H(2)15O at rest or during sequential vibration of either the left or the right hand or side of the mouth. RESULTS: PSA activation decreased significantly in the patients with blepharospasm both ipsilateral (-68%; p = 0.0004) and contralateral to the side of facial stimulation (-56%; p = 0.0009). Patients had a 31% lower mean contralateral PSA response to hand vibration and a 51% smaller right supplementary motor area response to left-hand vibration than normal subjects, but these differences did not reach statistical significance. CONCLUSIONS: Patients with blepharospasm have abnormal sensorimotor processing in response to lower face vibration. They may also have abnormal brain responses to stimulation of clinically uninvolved parts of the body, but this requires confirmation.

Respiratory syncytial virus-associated lower respiratory illnesses: possible influence of other agents. The Group Health Medical Associates.

Acute lower respiratory illnesses were prospectively investigated in a cohort of 1246 healthy infants who were enrolled at birth in the Tucson Children's Respiratory Study and followed through the first 3 years of life. Respiratory syncytial virus (RSV) infection was documented by culture, antigen detection or both in 276 episodes. In 21 (7.6%) of these 276, other viruses were simultaneously detected. Further serologic studies of 50 episodes in which RSV had been found increased the apparent viral codetection rate to 24%. When culture results for Chlamydia trachomatis and Mycoplasma pneumoniae were also considered, the rate of codetection was found to be 10.9% (30 of 276); this increased to 28% for the subgroup of episodes (14 of 50) that was further studied serologically. Illnesses associated with more than one agent were not significantly different from those involving RSV alone, with respect to month of onset, age at illness, illness type or duration of illness. We conclude that when RSV has been detected in previously healthy infants, routine searches for the concomitant presence of other viruses are usually not warranted.

Acute lower respiratory illnesses during the first three years of life: potential roles for various etiologic agents. The Group Health Medical Associates.

Lower respiratory tract illnesses (LRIs) occurring during the first 3 years of life among children enrolled in the Tucson Children's Respiratory Study have been studied for evidence of viral, mycoplasmal and Chlamydia trachomatis infections. This report examines those from whom adequate acute and convalescent sera were available at the time of the LRI. Two groups were compared: those in whom culture and/or antigen detection yielded an etiologic agent (N = 110); and those who did not (culture negative, N = 124). Seroconversions (> or = 4-fold titer rise) to respiratory syncytial virus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; or adenovirus were found in only 0 to 5% of the culture negative group. No significant differences between groups with regard to frequencies of seroconversion to influenza type C, parainfluenza virus type 4, human coronaviruses 229E and OC43 or cytomegalovirus were detected, which suggests that these agents may not be frequent primary causes of LRIs among otherwise healthy children. Significant differences in seroconversions to Epstein-Barr virus were detected, suggesting that Epstein-Barr virus may contribute to LRI morbidity; however, its exact role remains to be defined.

Age-related changes in mitogen-induced lymphocyte function from birth to old age.

This study examines the relationship between age and mitogen-induced lymphocyte blastogenesis. Lymphocytes were stimulated with PHA; Concanavalin A (Con A), and PWM in 156 normal, healthy subjects ranging in age from birth to 75 years. The findings indicate a gradual but significant decrease in PHA- and Con A-induced blastogenesis with increasing age. The decrease in Con A and PHA induced in vitro lymphocyte function begins in early childhood and young adulthood, respectively, and continues throughout the age range studied. In addition, there appears to be a decreased range of lymphocyte functional capacity among the 50-75-year-old subjects. The clinical and laboratory implications of these observations are discussed.

Rheumatoid factor activity by rate nephelometry correlated with clinical activity in rheumatoid arthritis.

The purpose of this study was to evaluate, prospectively, the clinical usefulness of the rate nephelometric method for determining rheumatoid factor (RF) activity, measured in International Units (IU), in patients with rheumatoid arthritis. These results were compared with those of standard latex agglutination titration. The overall correlation between clinical activity and RF activity measured by rate nephelometry and serologic titration are similar, i.e., r = 0.47 (P less than 0.001) and r = 0.43 (p less than 0.001), respectively. However, on an individual patient basis, the nephelometric determination appears to correlate better with disease activity and response to therapy than do titers. The RF activity measured in IU would give the clinician a more sensitive and precise tool with which to follow RF activity in individual patients with active disease.

The effect of lymphocyte recovery on lymphocyte typing results.

This study examines the relationship between percent recovery of lymphocytes and T- and B-cell typing results. Lymphocytes were recovered from heparinized whole blood by density gradient centrifugation. T- and B-cells were enumerated by spontaneous sheep rosetting and direct fluorescent antibody staining for surface immunoglobulin, respectively. The findings indicate that at low recovery levels ( less than 80%) there is a significant increase in variability of lymphocyte typing results and a significant increase in IgG-bearing B-lymphocytes. Possible explanations for these findings are discussed. These results suggest that lymphocyte typing results should be interpreted in relation to recovery level and that recovery levels of greater than or equal to 80% are desirable.

Application of pooled monoclonal antibodies for 1-hr detection of respiratory syncytial virus antigen in clinical specimens.

A fluorescein isothiocyanate-conjugated pool of monoclonal antibodies (MoAb) to respiratory syncytial virus (RSV) was prospectively evaluated for its utility as a direct, 1-hr test for the diagnosis of RSV infection. Direct nasopharyngeal swab smears collected from 109 infants and children with acute respiratory illnesses were studied and compared with results obtained by indirect immunofluorescence using bovine polyclonal anti-RSV antibody on eluted cells derived from pooled nasopharyngeal and throat swab specimens (a 2.5-3 hr procedure), and culture. The MoAb-direct smear method was at least 86%-89% sensitive and 95%-100% specific compared with either of the other procedures. Additional prospective evaluations, as well as retrospective studies on a selected bank of slides stored from the preceding year, established that this MoAb could also be used with confidence in testing where direct smears are not employed.

An eight-year study of the viral agents of acute gastroenteritis in humans: ultrastructural observations and seasonal distribution with a major emphasis on coronavirus-like particles.

During an 8-yr period, 862 stool specimens from patients with gastroenteritis were examined by electron microscopy after negative staining with 2% phosphotungstic acid (pH 6.5). Forty-one percent of the specimens submitted over an 8-yr period were determined to be positive for virus or viruslike particles belonging to one or more of seven morphologically distinct viral groups. Coronavirus-like particles (CVLPs) were present in 69.8% of the positive stool specimens. Membranous profiles containing "complement-type" holes (10 nm in diameter) were identified in some preparations containing CVLPs. The second most prevalent viral agent found in stool specimens was the rotavirus (17% of all positive stools). The incidence of other viruses identified in the survey were as follows: adenovirus 4.5%, picorna/parvovirus agents 2.9%, Norwalk-like agent 2.9%, astrovirus 1.9%, and calicivirus 0.5%. Unclassified small round viruses (approximately 25-30 nm in diameter) represented 0.5%. It was also determined that there was a seasonal distribution in excretion of all viruses except for CVLPs. A greater number of viruses were identified in the cooler, drier months of the year.

Efficacy and safety of a new bulk toxin of botulinum toxin in cervical dystonia: a blinded evaluation.

We investigated the efficacy and safety of botulinum toxin A (BTX) manufactured from a new bulk strain for the treatment of cervical dystonia. This was a single-blinded retrospective comparison of length of benefit, subjective improvement, and complications of treatment in 50 patients treated with the old form of toxin designated 79-11 and the new toxin strain BCB2024. The mean duration of benefit of the 79-11 strain and the BCB2024 strain were the same. Subjective efficacy, measured on a -4 to +4 scale, demonstrated no difference between the two strains. Dysphagia occurred in 12% of patients injected with the 79-11 strain and 14% of subjects injected with the BCB2024 strain. We also used a clinician's global assessment that incorporated the duration of benefit, subjective efficacy, and complications as a secondary analysis. There was no significant difference between the two forms of botulinum toxin A according to this scale. We conclude that the 79-11 strain and the BCB2024 strain offer similar peak efficacy duration of benefit, and adverse events.

Age-related changes in T- and B-lymphocyte subpopulations in the peripheral blood.

Quantitation of T and B lymphocytes in infants and children is an important test in the diagnosis of a suspected immuno-deficiency. Previous studies indicated that the absolute and relative numbers of lymphocyte subpopulations vary with age, but these data in the pediatric age group are incomplete and often contradictory. We reviewed the literature and investigated the relationship between age and lymphocyte subpopulations in healthy infants and children using common methods and recent methodologic improvements. We found that absolute numbers of T and B cells followed the same trend as the total lymphocyte count, which was elevated at birth, increased in the first six months, and then gradually decreased to adult levels at approximately 13 years of age. Compared with adult values, the percentage of B cells also was higher at birth and continued to increase for six months, followed by a gradual decrease to adult levels by late childhood or early adolescence. The percentage of T cells gradually increased to adult levels by the same age range.

Role of canine parainfluenza virus and Bordetella bronchiseptica in kennel cough.

The effect of Bordetella bronchiseptica upper airway colonization on the clinical, radiographic, serologic, pathologic, and pulmonary function changes caused by canine parainfluenza-2 virus (CPIV-2) infection was studied in 24 purebred Beagle pups (10.5 +/- 1.4 weeks old). Eight control dogs (group I) were not colonized or inoculated with CPIV-2. Of the 12 noncolonized dogs inoculated with CPIV-2 (group II), 9 developed antibody titers to CPIV-2 and 10 had clinical signs of infectious canine tracheobronchitis (kennel cough). Group I and group II dogs did not differ in radiographic findings or pulmonary function. Four group II dogs necropsied 1 to 5 days after clinical signs developed had laryngotracheobronchitis and bronchiolar inflammation not present at necropsy on 2 group I dogs. Four dogs had B bronchiseptica upper airway colonization and were inoculated with CPIV-2 (group III). All 4 group III dogs developed positive antibody titers, had clinical signs of kennel cough, and had radiographic changes. Pulmonary dynamic compliance was lower in group III than in group I or group II animals. Respiratory rate and tidal volume did not differ among the 3 groups. The 1 group III dog that was necropsied had changes similar to group II dogs with the addition of lobar bronchopneumonia. The present study indicates that asymptomatic B bronchiseptica colonization may effect the clinical, radiographic, and pulmonary function changes produced by CPIV-2 respiratory tract infections.

Comparison of direct and indirect immunofluorescence staining of clinical specimens for detection of respiratory syncytial virus antigen.

Immunofluorescence staining methods for respiratory syncytial virus antigen detection were compared. Of 50 specimens originally positive for respiratory syncytial virus by direct immunofluorescence and culture, 49 were positive by repeat direct immunofluorescence and 32 were positive by indirect immunofluorescence. Additional results obtained on specimens originally negative for respiratory syncytial virus by direct immunofluorescence, culture, or both indicate that direct immunofluorescence staining for respiratory syncytial virus antigen was more sensitive than was indirect immunofluorescence.

Variable susceptibility of mice to group B coxsackievirus infections.

Laboratory strains of group B coxsackievirus serotypes 1 to 6 were inoculated intraperitoneally into newborn mice of differing genetic backgrouns. Of the four genetic strains investigated, C3H mice appeared to be resistant to all six serotypes, whereas BALB/c mice were most susceptible. Swiss mice and a random-bred Swiss strain (COH) were intermediate in susceptibility. The findings underscore the fact that clinical isolation attempts and experimental studies involving group B coxsackieviruses must take into account both the virus strain used and the genetic background of the host. For clinical isolation of these viruses, the BALB/c mouse may be the most suitable of th strains tested.

Effects of systemic hypotension on postnatal intestinal circulation: role of angiotensin.

Systemic hypotension causes a greater degree of vasoconstriction in intestine from 3- than from 35-day-old postnatal swine. To determine the basis for this age-dependent difference, systemic hypotension (pressure reduction to approximately 50% of baseline) was induced by creating pericardial tamponade in postnatal swine instrumented to allow measurement of intestinal hemodynamics and oxygenation in vivo. Hypotension caused gut vascular resistance to increase 77 +/- 6% in 3-day-old subjects but only 18 +/- 3% in 35-day-old subjects. Prior blockade of alpha1-receptors with phentolamine, vasopressin receptors with [d(CH2)5,D-Phe2,Ile4,Ala9-NH2]AVP, or surgical denervation of the gut loop had no effect on hypotension-induced gut vasoconstriction. Losartan, which blocks angiotensin AT1 receptors, significantly attenuated hypotension-induced gut vasoconstriction in both age groups. BQ-610, which blocks endothelin ETA receptors, also limited the magnitude of vasoconstriction but only in younger subjects. This effect may have been consequent to an interaction between endothelin and angiotensin, inasmuch as a subpressor concentration of endothelin increased the contractile response to angiotensin in mesenteric artery rings. The substantial rise in 3-day-old gut vascular resistance was partly consequent to a locally mediated vasoconstriction that occurred in response to pressure and/or flow reduction during hypotension, as evidenced by the significant attenuation of this constriction when blood flow was held constant by controlled-flow perfusion to the gut loop during hypotension. Intestinal O2 uptake was compromised to a significantly greater degree in 3- than in 35-day-old subjects during hypotension. This difference was primarily due to the inability of younger intestine to increase O2 extraction in the face of reduced blood flow and may be mediated, in part, by an effect of angiotensin II on intestinal capillary perfusion.