Development of rostrocaudal dendritic bundles in rat thoracic spinal cord: analysis of cholinergic sympathetic preganglionic neurons.

Using monoclonal antibodies to choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP), we have analyzed the development of the dendritic bundles formed by cholinergic sympathetic preganglionic neurons (SPNs) in relationship to changes in the organization of glial fibers. In adult rat thoracic spinal cord, SPNs in the intermediolateral (IML) and central autonomic (CA) regions extend dendrites in both the mediolateral and rostrocaudal directions, forming a ladder-like pattern in horizontal sections of thoracic spinal cord. We report that, while the mediolateral dendrites form prenatally, the rostrocaudal dendritic bundles are not detected until at least a week later, during early postnatal life. The rostrocaudal dendrites develop rapidly during the first postnatal week, and achieve an adult-like pattern by postnatal day 14. The observed ontogenetic arrangements of dendritic bundles were correlated with the developing organization of astroglial processes with which they are intimately associated. While the appearance of mediolateral dendrites is consistent with the radial organization of glial in the embryonic spinal cord, the developmental time course of the rostrocaudal dendritic bundles coincides with the transformation of glial cells from this predominantly radial or transverse orientation to the randomly-oriented, stellate pattern of mature astrocytes. This temporal association suggests that ontogenetic changes in the organization of glial cells may contribute to the differential development of mediolateral and rostrocaudal dendritic patterns in the spinal cord.     

Gonadotrophin-releasing hormone agonist therapy for hirsutism is as effective as high dose cyproterone acetate but results in a longer remission

Both cyproterone acetate (CPA) and the gonadotrophin-releasing hormone agonist (GnRHa) have been shown to be effective for the treatment of hirsutism. We wished to compare the effectiveness of CPA in two standard doses with GnRHa and add-back therapy and to compare the length of remission after these treatments. A total of 60 hirsute hyperandrogenic women was assigned to the following treatment groups: CPA 2 mg with 35 microg of ethinylestradiol for 21 days each month (Diane group), CPA 50 mg, days 5-15, and ethinylestradiol 50 microg, days 5-25, each month (CPA group) or Decapeptyl 3.75 mg i.m. every 28 days with the addition of conjugated oestrogen 0.625 mg, days 1-21, and medroxyprogesterone acetate 10 mg, days 12-21 (GnRHa group). Hirsutism was graded by the Ferriman-Gallwey-Lorenzo (FGL) index and anagen hair shaft diameters and serum luteinizing hormone (LH) and testosterone were assessed before and every 3 months during and after treatment. All women were treated for 1 year with 1 year follow-up. At baseline hirsutism and endocrine patterns were similar in all groups. After one year of treatment, hirsutism decreased in all groups but the changes were greater (P <0.05) in the CPA and GnRHa groups than in the Diane group. Serum LH and testosterone were lowest in the GnRHa group. After withdrawal, hirsutism increased rapidly in the Diane and CPA groups and after 6 months, FGL scores and hair shaft diameters were similar to pretreatment values. In the GnRHa group, hirsutism increased more gradually and after 1 year of withdrawal, FGL scores and hair diameters were significantly (P <0.05) less than pretreatment values. Serum LH and testosterone increased rapidly in all three groups reaching pretreatment values by 6 months. These data suggest equal efficacy of the GnRHa and the high dose CPA regimen for the treatment of hirsutism in hyperandrogenic women. GnRHa with add-back treatment appears to result in a longer remission of hirsutism in comparison with CPA.      

Maxillary sinusitis in adults: an evaluation of placebo-controlled double-blind trials

BACKGROUND: In general practice, acute sinusitis is frequently diagnosed and treated with antibiotics. OBJECTIVE: This study aimed to determine the evidence for the effectiveness of antibiotic treatment in acute maxillary sinusitis in adults by assessing the methodological quality of placebo-controlled double-blind randomized trials. METHOD: An evaluation by four raters through a 35-item scoring-scale for internal and external validity of all placebo-controlled double-blind randomized trials on acute sinusitis found between January 1966 and July 1996. RESULTS: Eighty-five trials were excluded because they were not placebo-controlled, double-blind, randomized, or were carried out in patients with chronic sinusitis or in children. The three remaining trials were performed in different populations (one in general practice) between 1973 and 1978. Only one study claimed superiority of antibiotic treatment. Different inclusion criteria and major outcome measures were used by the authors. The reliability of major outcome events was reported poorly or not at all and in two studies outcome measures were clinically inappropriate. The studies scored 30-62% of the maximum attainable score for internal validity and 10-20% for external validity. CONCLUSION: The effectiveness of antibiotic treatment in acute maxillary sinusitis in a general practice population is not based sufficiently on evidence.      

Relation between toxicity and carcinogenesis in the kidney: an heuristic hypothesis

Cellular toxicity and cellular carcinogenesis are closely linked. In the kidney, this relationship has been emphasized by the recent discovery of a number of putatively non-mutagenic chemicals that result in acute and chronic toxicity and ultimately in carcinogenesis, especially in the male rat. Many, but not all such compounds, result in renal PTE phagolysosomal overload. At the same time, known metabolites of other carcinogens, e.g., HCBD and FBPA, result in acute renal injury and/or necrosis, followed by chronic tubular disease, interstitial nephritis, and ultimately carcinogenesis. A series of cell mechanisms have been suggested that lead from acute cell injury to altered control of cell division. These mechanisms appear to involve ion deregulation, (especially [Ca2+]i) resulting from a variety of continued injuries, (e.g., oxidative stress from inflammatory cells) and ultimately leading to altered gene expression.     

Recruiting future neuroscientists: what asking the recruits can teach us.

Many different strategies are used to recruit students into scientific research careers, including neuroscience research. These strategies are rarely based on knowledge about students; instead, activities are selected based on their ease of implementation. The goal of the LEARN Project is to encourage high school students into mental health science research using the theme of learning and memory. One intervention the authors developed is five Web-based biographies introducing students to contemporary neuroscientist role models studying learning and memory. To guide the design of this intervention, the authors created a survey to determine where students obtain career information and who and what influences their career selection. In a convenience sample of 124 students, the authors found that almost all students use the Internet for information about careers, in addition to consulting family members and teachers. Students' career selections are influenced most by family members, teachers, and people already in the field. The most important factors students look for in their future career are money, fun, and a good match between current interests and future careers. The data affirm the value of outreach efforts that go beyond students to include a broader audience of parents and teachers who play a critical role in career selection.     

Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors.     

Preventive care: do we practice what we preach?

We used insurance claims from enrollees in the Rand Health Insurance Experiment to determine the amount of selected components of preventive care received by a representative sample of the non-aged population in the United States and to determine whether insurance coverage was an important determinant of that amount. Only 45 percent of infants received timely immunization for DPT and polio; 93 per cent received some well child care by 18 months of age. In the three-year experimental period, only 4 per cent of adults had a tetanus shot, 66 per cent of women aged 17-44 and 57 per cent aged 45-65 received a Pap smear, and 2 per cent of women aged 45-65 had a mammogram. Cost sharing was associated with even less preventive care: 60 per cent of children on the free plan and 49 per cent on cost sharing plans received preventive care of any type. For adults, women on the free plan received more preventive care of several kinds, and those aged 45-65 received more Pap smears than those on cost-sharing plans. Even with free care, most enrollees did not receive adequate preventive care. Thus, free care alone, while significant, is not a sufficient incentive to providing recommended levels of preventive care. The average per person insurance charge for increasing the amount of preventive care to a level consistent with that recommended would be $22 for a complete set of immunizations by age 18 months, $9 for a Pap smear every three years, and $97 for a Pap test and mammogram every three years.     

Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls

We studied 14 patients with obsessive-compulsive disorder (OCD) by positron emission tomography and the fluorodeoxyglucose method, looking for abnormalities in local cerebral metabolic rates for glucose in brain structures that have been hypothesized to function abnormally in OCD. These patients were compared with 14 normal controls and 14 patients with unipolar depression. The patients with unipolar depression and OCD did not differ in levels of anxiety, tension, or depression. In OCD, metabolic rates were significantly increased in the left orbital gyrus and bilaterally in the caudate nuclei. This was apparent on all statistical comparisons with both controls and unipolar depression. The right orbital gyrus showed at least a trend to an increased metabolic rate in all comparisons. The metabolic rate in the left orbital gyrus, relative to that in the ipsilateral hemisphere (orbital gyrus/hemisphere ratio), was significantly elevated compared to controls and subjects with unipolar depression, and stayed high even with successful drug treatment. Though it was in the normal range in the morbid state, with improvement in OCD symptoms after drug treatment, the caudate/hemisphere metabolic ratio increased uniformly and significantly bilaterally. This ratio did not increase in patients who did not respond to treatment. Thus, OCD showed cerebral glucose metabolic patterns that differed from controls in both the symptomatic and recovered states.