Striatal dopaminergic abnormalities in human cocaine users.

OBJECTIVE: Previous human postmortem experiments have shown an abnormally high number of dopamine uptake sites in the striatum of chronic cocaine users, which might contribute to cocaine withdrawal symptoms such as depression and suicidality. Previous inconsistencies in results were perhaps related to selective radioligand affinity changes or a coexisting loss of dopamine neurons. METHOD: In the present study, binding of the cocaine analog [3H]WIN 35428 to the dopamine transporter was assayed in postmortem striatal samples from 15 cocaine-using subjects and 15 matched comparison subjects to determine whether there were differences in number of binding sites or in affinity. Binding to the vesicular monoamine transporter, a measure of total dopaminergic terminals, was also assessed by using the radioligand (+)-[3H]dihydrotetrabenazine (DTBZ). RESULTS: Striatal [3H]WIN 35428 binding sites were significantly more numerous in the cocaine users: the mean Bmax value was 9.0 fmol bound/microg protein (SD = 2.8) for the cocaine users but only 6.0 (SD = 1.7) for the comparison subjects. Severity of chronic cocaine use was significantly related to [3H]WIN 35428 binding level. [3H]DTBZ binding was significantly lower in the cocaine users (mean = 330 nCi/mg, SD = 42) than in the comparison subjects (mean = 374, SD = 68). CONCLUSIONS: The present results confirm that cocaine users have a high number of dopamine transporter binding sites on dopaminergic neurons, despite an apparent low number of total dopamine terminals. These abnormalities may contribute to the abnormalities in subjective experience and behavior characteristic of chronic cocaine abusers.

Epidemiology of high grade prostatic intraepithelial neoplasia.

The prevalence of high grade prostatic intraepithelial neoplasia (HGPIN), the age at which this lesion starts and the potential racial or ethnic differences in its distribution are poorly documented. HGPIN is becoming increasingly implicated as a premalignant lesion for clinically significant prostatic carcinoma (PCa) with mounting evidence linking it to carcinoma according to morphologic immunohistochemical and recent genomic studies. We describe our experience with the age and race distribution of HGPIN resulting from two study populations of African-American (AA) and Caucasian (C) males. The first component of this report describes an autopsy study aimed at determining the prevalence of latent PCa and HGPIN in AA and C men 20 years of age or older; 370 (218 AA and 152 C) consecutive step-sectioned, totally embedded prostate glands were microscopically evaluated and mapped for HGPIN and PCa. HGPIN was first identified in the third decade and increased steadily with age. Latent PCa increased steadily with age with no significant difference in the prevalence between AA and C males in any age group (3rd to 8th decades). HGPIN, on the other hand, was more prevalent in AA men with 18, 31, 69, 78 and 86% in their 4th, 5th, 6th, 7th and 8th decades harboring the lesion. The corresponding figures for C men were 14, 21, 38, 50 and 63% respectively. When HGPIN was quantitated as focal and extensive according to the degree of glandular involvement, extensive HGPIN appeared earlier in AA males under 60 years of age compared to C males cohort. The difference in age distribution appeared to follow a chronological pattern, with HGPIN in AA preceding that of C males by approximately a decade. The second component of this report describes a surgical series of 345 consecutive radical prostatectomies from patients (155 AA and 190 C) with clinically localized PCa, which were thoroughly evaluated microscopically by two urologic pathologists. Similar to the findings in the autopsy study, extensive HGPIN was more prevalent in AA men 60 years of age or younger (57% vs. 33%). In both races, the mean percentage of the gland involved by HGPIN decreased with advancing age in contrast to the mean tumor volume that increased with patient age. These findings indicating a different prevalence of HGPIN in the two racial groups may help explain the higher incidence of prostatic cancer in African-Americans.

High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases.

The relationship of prostatic intraepithelial neoplasia (PIN) and invasive carcinoma of the prostate is not fully understood. It is generally accepted that HGPIN is a probable preinvasive malignant change or at least a marker lesion for carcinoma. The prevalence of HGPIN in younger men is not known. Two hundred and forty nine entirely processed prostates from men aged 20-69 were thoroughly evaluated for the presence of PIN and carcinoma. The histologic diagnosis of all positive cases was confirmed by two pathologists. Our results are summarized as follows: Seventy seven percent of the prostates with HGPIN harbored adenocarcinoma, whereas the frequency of cancer in prostates without HGPIN was 24%. HGPIN was encountered in 0, 5, 10, 41 and 63% of men in the 3rd, 4th, 5th and 7th decades, respectively. The corresponding figures for invasive carcinoma were 2, 29, 32, 55, and 64% respectively.

The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients.

The incidence of clinically detected prostate cancer is increasing with more frequent diagnosis in younger male patients. Whether this represents a genuine increase in incidence or earlier detection is not clear. To understand better the evolution and early changes of prostate cancer we evaluated 152 prostate glands from young male patients 10 to 49 years old. Of the prostates 98 were from African-Americans and 54 were from white patients. Prostatic intraepithelial neoplasia was identified in 0%, 9%, 20 and 44%, and small foci of histological cancer in 0%, 0%, 27% and 34% of the male patients in the second, third, fourth and fifth decades of age, respectively. The majority of the cases of prostatic intraepithelial neoplasia were of low grade. High grade prostatic intraepithelial neoplasia, found in 5 prostates, was first identified in the fifth decade. All 5 cases occurred in prostates containing histological carcinoma. Incidental carcinoma was detected with a similar frequency in white and black patients. The cancerous foci were of similar size with a tendency for cancer in black patients to be multifocal, particularly in those in the fifth decade. We conclude that prostatic intraepithelial neoplasia and histological cancers are surprisingly common in young male patients of both races. The evolution of prostatic intraepithelial neoplasia and focal histological cancers is not clear but it appears to present several decades earlier than clinically detected carcinoma. The natural history of prostate cancer must encompass many more years (decades) than has been previously realized. In addition, the initiating events leading to clinically relevant prostate cancers likely occur at a remarkably young age.

Strabismus in children with cerebral palsy.

A group of 238 patients with cerebral palsy were identified of whom 108 could be studied through their charts. Only 20 of these patients had strabismus. Of this group, 10 received no surgical therapy. In these patients followed up to a period of four years, no evidence of significant change in the strabismic deviation was found. Patients who were treated by medical and optical means alone did not show evidence of improvement. Surgical therapy was effective in providing a cosmetically acceptable result. Surgery was performed between two and one-half and 13 years of age in eight patients, with an average age of surgery of 6.5 years. The results which we obtained are comparable to those obtained by others at an earlier age. It does not appear that the age of surgery affects the ultimate cosmetic nor functional outcome in children with cerebral palsy.