Prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infection among Spanish drug users measured by HTLV-1 assay and HTLV-1 and -2 assay. HTLV-1 and HTLV-2 Spanish Study Group.

The prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infection in 1992 and 1993 was determined by testing 2,152 specimens from injection drug users living in 11 geographic areas in Spain. Results obtained by an authentic HTLV-1 and -2 test were compared with those obtained by an HTLV-1 assay. HTLV infection was identified in 7 of 11 regions, with an overall prevalence of 2.5% (range, 0.4 to 11.5%). Fourty-four (81%) of 54 subjects were infected with HTLV-2; the viral strains in the remaining 10 subjects could not be serologically typed. Underestimation of HTLV infection because of the low sensitivities of HTLV-1 enzyme immunoassays for HTLV-2 antibody was relatively low (< 20%). Therefore, previous epidemiologic findings generated with HTLV-1 enzyme immunoassays appear to be reasonably accurate. Our results suggest that the rate of HTLV infection may have been increasing recently among Spanish drug users.     

Direct sequence evaluation of the major outer membrane protein gene variant regions of Chlamydia trachomatis subtypes D'', I'', and L2''.

The nucleotide sequences of variable segments (VS) 1, 2, and 4 for the major outer membrane protein gene (omp1) of Chlamydia trachomatis were determined for serologically defined subtypes D', I', and L2'. Asymmetric DNA amplification was used to produce single-stranded DNA for direct sequencing. Amino acid substitutions were detected in VS1, VS2, and VS4 for I', in VS2 for L2', and in VS4 for D'. DNA sequencing of omp1 variant regions may be an important method for evaluating the molecular epidemiology of Chlamydia spp.     

Co‐occurring medical conditions in adults with Down syndrome: A systematic review toward the development of health care guidelines. Part II

Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. Many of these conditions are of public health importance with the potential to develop screening recommendations to improve clinical care for this population. Our workgroup previously identified and prioritized co‐occurring medical conditions in adults with DS. In this study, we again performed detailed literature searches on an additional six medical conditions of clinical importance. A series of key questions (KQ) were formulated a priori to guide the literature search strategy. Our KQs focused on disease prevalence, severity, risk‐factors, methodologies for screening/evaluation, impact on morbidity, and potential costs/benefits. The available evidence was extracted, evaluated and graded on quality. The number of participants and the design of clinical studies varied by condition and were often inadequate for answering most of the KQ. Based upon our review, we provide a summary of the findings on hip dysplasia, menopause, acquired cardiac valve disease, type 2 diabetes mellitus, hematologic disorders, and dysphagia. Minimal evidence demonstrates significant gaps in our clinical knowledge that compromises clinical decision‐making and management of these medically complex individuals. The creation of evidence‐based clinical guidance for this population will not be possible until these gaps are addressed.     

Early Response of Lung to Low Levels of Ozone

The epithelial response in the terminal bronchioles and alveoli was examined after exposure to approximately 0.5 and 0.9 ppm ozone (O₃). Loss of ciliated cells from the terminal bronchiole was pronounced after 6 to 10 hours of exposure; however, nonciliated cells were resistant to injury from O₃. In contrast, type 1 alveolar lining cells were very sensitive to O₂ and were severely damaged or removed from significant areas of the proximal alveoli after as little as 2 hours of exposure to 0.5 ppm. The basement lamina was left devoid of an epithelium with the exception of type 2 cells, which were very resistant and retained a relatively normal appearance. Under continuous exposure, repair of the lesion area was accomplished in approximately 48 hours through proliferation of the type 2 cells. The new cells were cuboidal at first but subsequently became more squamous in appearance. Exposure for 8 to 10 hours followed by residence in clean air resulted in a proliferative response at 48 hours, about equal to that observed after continuous exposure.     

Organization of the central control of muscles of facial expression in man

The capacity of the vascular endothelium locally to release tissue-type plasminogen activator (t-PA) is critical for effective endogenous fibrinolysis. We determined the influence of ageing and regular aerobic exercise on the net release of t-PA across the human forearm in vivo using both cross-sectional and intervention approaches. First, we studied 62 healthy men aged 22-35 or 50-75 years of age who were either sedentary or endurance exercise-trained. Net endothelial release rates of t-PA were calculated as the product of the arteriovenous concentration gradient and forearm plasma flow to intra-arterial bradykinin and sodium nitroprusside. Second, we studied 10 older (60 ± 2 years) healthy sedentary men before and after a 3 month aerobic exercise intervention. Net endothelial t-PA release was significantly blunted with age in the sedentary men. At the highest dose of bradykinin the increase in t-PA antigen release was ≈35 % less (   P < 0.05  ) in the older (from −1.0 ± 0.4 to 37.8 ± 3.8 ng (100 ml tissue)⁻¹ min⁻¹) compared with young (from 0.1 ± 0.6 to 56.6 ± 9.2 ng (100 ml tissue)⁻¹ min⁻¹) men. In contrast, the endurance-trained men did not demonstrate an age-related decline in the net release of t-PA antigen. After the exercise intervention, the capacity of the endothelium to release t-PA increased ≈55 % (   P < 0.05  ) to levels similar to those of the young adults and older endurance-trained men. Regulated endothelial t-PA release declines with age in sedentary men. Regular aerobic exercise may not only prevent, but could also reverse the age-related loss in endothelial fibrinolytic function.     

Diagnosis of Neisseria gonorrhoeae infections in women by using the ligase chain reaction on patient-obtained vaginal swabs.

The increased sensitivities of nucleic acid amplification tests such as ligase chain reaction (LCR) have the potential to simplify specimen collection for gonorrhea diagnosis. In this study patients took their own vaginal swab specimens for gonorrhea culture and LCR testing. Immediately following specimen collection by patients, a trained clinician obtained endocervical swab specimens for the same tests. By using LCR to diagnose gonorrhea, 54 (17.5%) of 309 patients had positive tests. Forty-five patients with positive cervical LCR tests also had positive vaginal LCR tests; for one patient, only a cervical LCR specimen was positive, and for eight patients, only vaginal specimens were positive. For specimens from patients whose gonorrhea cultures were positive, all vaginal swab specimens were positive by LCR and 42 (91%) of 46 cervical swab specimens were positive by LCR. LCR-positive specimens from eight patients with negative cultures (four with positive vaginal specimens only, one with a positive cervical specimen only, and three with positive vaginal and cervical specimens) were further evaluated with unrelated probe sets for gonococcal pilin B. Following resolution of the discrepancies between culture-negative and LCR-positive specimens, a diagnosis of gonorrhea could be confirmed for 52 of 54 patients with positive LCR tests. LCR testing with vaginal swabs was 100% sensitive and 99.6% specific and had a positive predictive value of 98.1% and a negative predictive value of 100%. In this study LCR testing of vaginal swab specimens obtained by patients themselves was significantly more sensitive for gonorrhea diagnosis of women than cervical LCR or culture (100% versus 84.6% for cervical LCR or culture; Mantel-Haenszel chi-square test result, 8.58; P = 0.003).     

The tendon organs of cat medial gastrocnemius: significance of motor unit type and size for the activation of Ib afferents.

1. Histological and histochemical studies suggest that each tendon organ in a mixed mammalian muscle should be particularly responsive to the contraction of a discrete number of motor units (ca. ten to fifteen), each with differing mechanical properties. This report describes physiological experiments that demonstrate this arrangement for the tendon organs of cat medial gastrocnemius. 2. No correlations could be found between the intensity of discharge of a single tendon organ and the contraction strengths of motor units whose contraction excited the receptor. Tendon organs were found to be as responsive to contraction of small slow twitch units as they were to contraction of larger fast twitch units. Taking the data as a whole, the apparent sensitivity of the receptors during motor unit contractions (pps/force recorded at the tendon) was inversely related to the contraction strengths of the motor units. 3. These findings are discussed in relation to recent evidence on the territory of single motor units in medial gastrocnemius and the force producing capabilities of their individual muscle fibres. It is concluded that in general each motor unit, whose contraction excites a given receptor, contributes one muscle fibre to the receptor capsule. Further, it appears that the various excitatory effects of those muscle fibres inserting into a given receptor capsule are not simply related to their relative contraction strengths but also depend on the details of the mechanical coupling between each fibre and the Ib afferent receptor endings. 4. The results of an ensemble analysis show that despite the lack of correlation between the intensity of tendon organ discharge and the force developed at the tendon during contraction of different motor units, a correlation does appear when the responses of several tendon organs and the forces developed by the motor units which excite them are summed progressively. This finding has implications for the recruitment order of motor units in that the profile of the collective Ib response is shown to differ according to whether motor unit forces are summed randomly or in order of increasing contraction strengths.     

Microheterogeneity of Neisseria lipooligosaccharide: analysis of a UDP-glucose 4-epimerase mutant of Neisseria meningitidis NMB.

Neisseria meningitidis is the etiologic agent of epidemic bacterial meningitis. Lipooligosaccharide (LOS) is a principal virulence factor associated with the organism, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of LOS has demonstrated that there is considerable microheterogeneity in the molecule. To begin our understanding of the nature of this heterogeneity, we identified a Tn916-generated LOS mutant of N. meningitidis NMB (serotype L3, monoclonal antibodies 3F11+, 6B4+, and 4C4-) that was designated NMB-SS3 (monoclonal antibodies 3F11-, 6B4-, and 4C4+). The transposon insertion was localized to the amino terminus of the functional copy of the UDP-Glc 4-epimerase gene (galE). UDP-Glc 4-epimerase (EC 5.1.3.2) activity was present in N. meningitidis NMB but not in NMB-SS3, indicating that the Tn916 insertion had abolished this activity. Mass spectrometric analysis of the LOS from strain NMB revealed multiple species of LOS, which is consistent with extensive microheterogeneity. While the most predominant structure was consistent with a terminal lacto-N-neotetrose structure found in other strains of N. meningitidis, Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4Glc-->(GlcNAc)-->Hep2PEA-->KDO2 (where Hep is heptose, PEA is phosphoethanolamine, and KDO is 2-keto-3-deoxymannooctulosonic acid), structures containing repetitive hexoses which are not precursors of this structure were also identified. Compositional analysis of LOS from strain NMB-SS3 revealed that there were no galactoses present in the structure. Mass spectrometric analysis of O-deacylated LOS revealed the presence of multiple species, with the predominant LOS species in this mutant strain formed by the Hex-->(HexNAc)-->Hep2PEA-->KDO2 (where Hex is hexose and HexNAc is N-acetylhexosamine) structure. However, LOS structures with repetitive hexoses, e.g., Hexn-->(HexNAc)-->Hep2PEA-->KDO2 (n = 2, 3, or 4), emanating from one or both heptoses were also identified. Since this mutant cannot synthesize UDP-Gal, these structures must repetitive glucoses. These data suggest that NMB has a glycosyltransferase capable of polymerizing glucose moieties as an alternative biosynthetic pathway to the wild-type lacto-N-neotetrose structure.     

Comparison of isolates of Neisseria gonorrhoeae causing meningitis and report of gonococcal meningitis in a patient with C8 deficiency.

We studied a previously healthy 20-year-old woman who presented with gonococcal meningitis. The gonococcal isolate, HT-1, was prototrophic by auxotyping, was protein I serovar IB-1, and agglutinated with wheat germ lectin. This isolate differed from the proline-requiring, serovar IA-1 and IB-4, wheat germ-agglutination-negative gonococcal isolates recovered from three patients during a recent outbreak of gonococcal meningitis in Philadelphia. HT-1 was killed by normal pooled human sera (greater than or equal to 98% at 30 min) but not effectively killed by the convalescent-phase sera of the patient (greater than 30% survival at 30 min). Similar results were obtained when mucosal and cerebrospinal fluid isolates from a Philadelphia patient were exposed to these sera, but mucosal and blood isolates from another Philadelphia case showed increased resistance to killing by normal pooled human sera. Further characterization revealed multiple differences in outer membrane and cellular proteins and lipopolysaccharide between case isolates. Absence of the L8 lipopolysaccharide epitope was noted for all isolates. Sera of our patient were found to have low total hemolytic complement (CH100 = 21 U/ml; normal = 55 to 100 U/ml) due to deficiency of C8 (C8 less than 1,000 CH50 U/ml; normal = greater than or equal to 16,000 CH50 U/ml). This is the first reported case of gonococcal meningitis occurring in a patient with a terminal-complement deficiency. Gonococcal meningitis is a rare complication of gonococcal bacteremia. Both defects in host defenses (e.g., terminal-complement deficiency) and organisms with unusual virulence appear to contribute to the pathogenesis of this complication of gonococcal bacteremia.