Absence of antibody production in patients treated with botulinum A toxin

To test the possibility of the formation of an antibody to botulinum A toxin after multiple injections of this potent neurotoxin, we collected serum samples from 28 patients who received 57 doses. These injections over a nine-month period with as much as 50 units per injection formed no detectable antibody.     

Polyamines modulate the binding of GABAA-benzodiazepine receptor ligands in membranes from the rat forebrain.

The effects of spermine, spermidine and putrescine on the binding of the GABAA-benzodiazepine receptor complex were examined in the hippocampus and frontal cortex membranes of the rat. The results demonstrated modulatory effects of polyamines on the binding of diazepam and flunitrazepam but not on that of GABA, muscimol and Ro 15-1788. When membranes were prepared without detergent, the polyamines enhanced the binding of diazepam. However, while the binding capacity increased after homogenization in the presence of the non-ionic detergent Triton X-100, the polyamines did not enhance the binding but inhibited the binding of diazepam and flunitrazepam at greater concentrations. Considered together with other studies, the present findings indicate that polyamines can modulate the binding characteristics of several different neurotransmitter receptor-ionophore complexes.     

Extradural lymphoma presenting as an acute surgical emergency

Extradural lymphoma can present as an acute neurosurgical emergency. The clinical presentation and radiological appearance may suggest epidural hematoma or meningioma. Lymphoma should be considered as a rare but possible diagnosis before operation. High resolution computed tomography using direct coronal imaging with and without contrast enhancement may aid in suggesting the correct preoperative diagnosis.     

Altered interleukin-2 production in schizophrenia: association between clinical state and autoantibody production.

Mitogen-stimulated interleukin-2 (IL-2) production was measured in 122 patients who met Research Diagnostic Criteria for schizophrenia and 98 normal control subjects. The presence of autoantibodies against seven common antigens was also determined. There was no relationship between the presence of circulating autoantibodies and IL-2 production in control subjects. In patients, however, autoantibody-positive, acutely ill patients had significantly lower IL-2 production as compared with other patients and control subjects. Never-medicated patients showed the same trends for decreased IL-2 production in association with autoantibodies. These data suggest that decreased IL-2 production is associated with acute illness in schizophrenic patients who produce autoantibodies, a trait known to be associated with increased vulnerability to autoimmune disease.     

Assessment of 5α-reductase activity in hirsute women: comparison of serum androstanediol glucuronide with urinary androsterone and aetiocholanolone excretion

OBJECTIVE Recent evidence suggests that androstanediol glucuronide (AG), a metabolite of dihydrotestosterone (DHT) formed in skin, is frequently elevated in hirsute women, presumably reflecting enhanced 5a-reductase activity. An alternative method of demonstrating 5a-reductase activity is the androsterone (A)/aetiocholano-lone (E) ratio in urine. A and E are the 5α- and 5β- reduced metabolites, respectively, of androstenedione, which is the principal metabolite of dehydroepiandrosterone (D). Although serum AG and the urinary A/E ratio have both been considered valid methods for assessing 5α-reductase activity, the two have not been previously compared in hirsute women. The present study was undertaken to assess 5a-reductase activity in hirsute patients as determined by these two different methods. PATIENTS AND MEASUREMENTS We surveyed 47 untreated women (ages 17–33) with various degrees of hirsutism. Serum testosterone, bioavailable testosterone, dehydroepiandrosterone sulphate, and AG were determined. Additionally, A, E and D were measured in 24-hour collections of urine. RESULTS For the 47 women, 37 had elevated blood levels of AG (17.4 ± 2.2, mean±SEM; normal <8 nmol/l), but only 18 of these had an increased urinary A/E ratio (> 1.5). All but one of the remainder had elevated urinary and/or serum androgen levels. Overall, no significant correlation between AG and A/E was observed. There was a highly significant correlation between AG in serum and A in urine (r= 0.82, P<0 001). AG was also positively related to dehydroepiandrosterone sulphate (r= 0.64; P< 0.005), bioavailable testosterone (r= 0.6; P<0001), aetiocholanolone (r= 0.58; P<0 001) and total testosterone (r= 0.52; P& 0.01). In contrast, A/E was not significantly related to androgen production. CONCLUSIONS There is a poor correlation between AG and the A/E ratio in hirsute women. Although AG may be raised by increased 5α-reductase activity, it is probably also affected by the presence of elevated androgens regardless of 5α-reductase activity.     

Unannounced simulated patients' observations of physician STD/HIV prevention practices.

Studies describing sexually transmitted disease (STD) and human immunodeficiency virus (HIV) prevention practices of primary care physicians have relied on physician or patient reports. This study describes physician STD/HIV prevention practices as observed by unannounced simulated patient evaluators (SPEs). SPEs visited sixty-five primary care physicians. Each SPE portrayed a sexually active female, new to the area, requesting a consultation on STD prevention. One-third of the physicians in the study asked no risk questions, and over 80% failed to ask the SPE specifically about her sexual practices. Most physicians discussed the risks of STDs and HIV and covered basic recommendations (use condoms and know partners better); however, few physicians provided any individualized information or advice about safer sexual practices and the specifics of condom use, such as how to use them or what kind to use. These observations support the low rates of STD/HIV prevention indicated in physicians' self-report and further identify specific deficiencies in the thoroughness of their risk assessment and preventive counseling practices.     

Mechanism of Pseudomonas aeruginosa persistence during treatment with broad-spectrum cephalosporins of lung infections in patients with cystic fibrosis.

Beta-lactam resistance in Pseudomonas aeruginosa detected only during ceftazidime therapy of cystic fibrosis patients was studied. Evaluation of resistant and susceptible isolates from one patient and resistant laboratory derivatives indicated that elevated beta-lactamase levels were the primary determinant of resistance. Susceptible isolates outgrew resistant isolates on antibiotic-free medium.     

Spontaneous ovarian hyperstimulation mimicking an ovarian tumour

Ovarian hyperstimulation syndrome in a spontaneous singletonpregnancy is exceedingly rare. We report a case of ovarian hyperstimulationpresenting as bilateral ovarian masses in association with spontaneouspregnancy, occurring in a woman with disturbed liver function.A possible mechanism is discussed.     

Protection from pathogenic SIV challenge using multigenic DNA vaccines

To assess DNA immunization as a strategy for protecting against HIV infection in humans, we utilized SIVmne infection of Macaca fascicularis as a vaccine challenge model with moderate pathogenic potential. We compared the efficacy of DNA immunization alone and in combination with subunit protein boosts. All of the structural and regulatory genes of SIVmne clone 8 were cloned into mammalian expression vectors under the control of the CMV IE-1 promoter. Eight M. fascicularis were immunized twice with 3 mg of plasmid DNA divided between two sites; intramuscular and intradermal. Four primed macaques received a further two DNA immunizations at weeks 16-36, while the second group of four were boosted with 250 microg recombinant gp160 plus 250 microg recombinant Gag-Pol particles formulated in MF-59 adjuvant. Half of the controls received four immunizations of vector DNA; half received two vector DNA and two adjuvant immunizations. As expected, humoral immune responses were stronger in the macaques receiving subunit boosts, but responses were sustained in both groups. Significant neutralizing antibody titers to SIVmne were detected in one of the subunit-boosted animals and in none of the DNA-only animals prior to challenge. T-cell proliferative responses to gp160 and to Gag were detected in all immunized animals after three immunizations, and these responses increased after four immunizations. Cytokine profiles in PHA-stimulated PBMC taken on the day of challenge showed trends toward Thl responses in 2/4 macaques in the DNA vaccinated group and in 1/4 of the DNA plus subunit vaccinated macaques; Th2 responses in 3/4 DNA plus subunit-immunized macaques; and Th0 responses in 4/4 controls. In bulk CTL culture, SIV specific lysis was low or undetectable, even after four immunizations. However, stable SIV Gag-Pol- and env-specific T-cell clones (CD3+ CD8+) were isolated after only two DNA immunizations, and Gag-Pol- and Nef-specific CTL lines were isolated on the day of challenge. All animals were challenged at week 38 with SIVmne uncloned stock by the intrarectal route. Based on antibody anamnestic responses (western, ELISA, and neutralizing antibodies) and virus detection methods (co-culture of PBMC and LNMC, nested set PCR- of DNA from PBMC and LNMC, and plasma QC-PCR), there were major differences between the groups in the challenge outcome. Surprisingly, sustained low virus loads were observed only in the DNA group, suggesting that four immunizations with DNA only elicited more effective immune responses than two DNA primes combined with two protein boosts. Multigenic DNA vaccines such as these, bearing all structural and regulatory genes, show significant promise and may be a safe alternative to live-attenuated vaccines.