Long-term followup of subclinical human papillomavirus infection treated with the carbon dioxide laser and intraurethral 5-fluorouracil: a treatment protocol

We evaluated 162 high risk male patients for the presence of subclinical anogenital human papillomavirus infection with magnified penile surface scanning. Infected patients were treated as outpatients with the carbon dioxide laser under local anesthesia. Of the patients 43 were followed for a mean of 8.7 months or 2.1 treatments after the initial treatment (range 3 to 30 months). A subset of 10 patients was followed for more than 20 months or 6.2 treatments. To date a 51% recurrence rate has been observed in the over-all population and a 50% recurrence rate was noted in the 20-month followup population. In a separate arm of this study a small number of patients (15) with deoxyribonucleic acid typed subclinical intraurethral disease plus subclinical skin lesions were treated with topical carbon dioxide laser therapy for the penile lesions and adjuvant intraurethral 5% 5-fluorouracil. Mean followup in the group was approximately 4 months. The addition of intraurethral therapy in this positive human papillomavirus reservoir group had no significant effect on the high rate of human papillomavirus recurrence.     

A pharmacokinetic comparison of the corn oil versus microemulsion gelcap formulation of cyclosporin used de novo after renal transplantation

The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose to renal allograft rejection. The present study served to compare the time required to achieve therapeutic CyA concentrations after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor the CyA-ME group adequately absorbed the drug during days 0–2, from day 3 to 4 patients in the CyA-ME group showed significantly greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (C_av) values ( ≥ 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de novo administration of CyA-ME than with CyA-GC. Received: 13 September 1996 Accepted: 7 January 1997     

Down's syndrome and the acquisition of phonology by Cantonese-speaking children

ABSTRACT. The phonological abilities of two groups of 4–9-year-old intellectually impaired Cantonese-speaking children are described. Children with Down's syndrome did not differ from matched non-Down's syndrome controls in terms of a lexical comprehension measure, the size of their phoneme repertoires, the range of sounds affected by articulatory imprecision, or the number of consonants, vowels or tones produced in error. However, the types of errors made by the Down's syndrome children were different from those made by the control subjects. Cantonese-speaking children with Downs syndrome, as compared with controls, made a greater number of inconsistent errors, were more likely to produce non-developmental errors and were better in imitation than in spontaneous production. Despite extensive differences between the phonological structures of Cantonese and English, children with Downs syndrome acquiring these languages show the same characteristic pattern of speech errors. One unexpected finding was that the control group of non-Down's syndrome children failed to present with delayed phonological development typically reported for their English-speaking counterparts. The argument made is that cross-linguistic studies of intellectually impaired children's language acquisition provide evidence concerning language-specific characteristics of impairment, as opposed to those characteristics that, remaining constant across languages, are an integral part of the disorder. The results reported here support the hypothesis that the speech disorder typically associated with Down's syndrome arises from impaired phonological planning, i.e. a cognitive linguistic deficit.     

Familial Parkinson's disease: possible role of environmental factors

We report here six families with Parkinson's disease in whom the onset of symptoms tended to occur at approximately the same time irrespective of the age of the patient. The mean difference in the time of onset in different generations was 4.6 years while the mean difference in age of onset in children and parents was 25.2 years. We construe this pattern of age separation within families as suggestive of an environmental rather than genetic cause. Support for this view derives from the lack of correlation between occurrence of the disease and the degree of consanguinity. We conclude that our findings are in accord with the hypothesis which attributes the cause of some cases of Parkinson's disease to early, subclinical environmental damage followed by age-related attrition of neurons within the central nervous system.     

Prevention of collagen-induced arthritis (CIA) by treatment with polyethylene glycol-conjugated type II collagen; distinct tolerogenic property of the conjugated collagen from the native one

Administration of a soluble protein into animals prior to challenge immunization induces immunological tolerance which is specific for the protein. In addition, chemical modification of proteins with polyethylene glycol (PEG) has been reported to convert the immunogenic proteins to become tolerogenic. However, differences in tolerogenic properties between PEG-modified proteins and the native counterparts have never been analysed. The ability of PEG-conjugated type II collagen (PEG-CII) to attenuate CIA, an animal model for rheumatoid arthritis, was compared with the native unconjugated CII. Groups of DBA/1 J mice were treated weekly with i.p. injections with PEG-CII, native CII, or vehicle alone for 3 weeks, before they were challenged with CII in adjuvants. The induction of tolerance was confirmed in both PEG-CII- and CII-pretreated mice when suppression of lymph node T cell proliferation in response to CII was noted. The degrees of suppression of T cell proliferation were comparable between the two pretreated groups. However, induction of arthritis and production of IgG anti-CII antibody were more markedly suppressed in PEG-CII-pretreated mice than in native CII-pretreated mice, although the severity of arthritis and antibody levels in the latter group were also lower than in control mice. IgG2a and IgG2b antibody levels were equally suppressed in the two pretreated groups, whereas the IgG1 level was significantly lower in the PEG-CII-pretreated group than in the native CII-pretreated group. The results provide the first evidence that attachment of PEG to CII renders the protein more tolerogenic.     

Release of histamine in whole blood by oxygen radicals: Division between specific and unspecific processes

Oxygen derived free radicals are involved in many pathological processes such as postischemic reperfusion injuries, hepatotoxicity of drugs and inflammatory processes. Thereby these oxygen radicals induce lipid peroxidation and perturbation of cellular membranes. The aim of our present study was to determine whether oxygen radicals generated by the xanthine oxidase/hypoxanthine system cause a release of histamine in human blood cell cultures. Stimulation of blood cell cultures with oxygen radicals induced a histamine liberation which was mainly due to calcium independent processes during the first 30 min, whereas then calcium requiring processes took part in the release of histamine. The regulation of the leukocyte selectin LECAM-1 was altered by oxygen radicals whereas histamine, which is known to modulate vascular selectin expression, did not affect the expression of LECAM-1. Our data indicate that oxygen radicals induce a direct calcium independent release of histamine which is due to membrane pertubating processes during the first phase but also induce a specific reaction leading to a further indirect histamine liberation which is probably mediated by PAF.accepted by W. LorenzThe first two authors contributed equally to this paper.     

Case-control study of late onset "probable Alzheimer's disease"

A case-control study was conducted on 64 cases of "probable Alzheimer's disease" with late onset of illness (after age 70 years) and 64 controls matched by age (+/- 3 years), race, and sex. Information was obtained on birth order, lifetime medical and surgical history, personal characteristics, exposure to toxins and animals, and a family history of various illnesses. None of the variables studied, including family history of dementia, reached statistical significance. An antecedent history of head trauma with loss of consciousness, though not statistically significant, was more frequently found in cases than in controls.