The structural relations between nerve fibres and muscle cells in the urinary bladder of the rat

Summary Intramuscular nerve fibres in the bladder of adult female rats were investigated by means of serial sections. The following observations were made. (1) Upon penetrating into the musculature the nerve bundles branch repeatedly, and almost all turn into single fibres; their axons become varicose, the Schwann cell sheath is attenuated, incomplete or absent, and the separation between axonal membrane and muscle cell membrane is reduced to tens of nanometres. (2) All single axons, and some of those within bundles, are varicose, but the characteristic of being varicose is expressed by degrees, and is not an all-or-none state. (3) Varicosities contain vesicles (mostly of the agranular type), microtubules (with little connection with the axolemma or the vesicles), some neurofilaments (scarce or absent in the best developed varicosities), mitochondria (whose size is on average smaller than those of the perikaryon, and a minute amount of endoplasmic reticulum. (4) Terminal varicosities, the true anatomical ending of an axon, are often devoid of Schwann cell sheath, are packed with vesicles, rarely contain microtubules or neurofilaments, and lie close to a muscle cell: the gap is often reduced to 10 nm. (5) Schwann cells accompany the axons within the muscle strands. Unlike the area of the axonal profiles, the area of glial sheath changes little along the length of the nerve fibre, except towards its end. (6) The Schwann cell sheath around a varicosity is often incomplete; the area of the axolemma thus exposed is covered by the basal lamina, and is here referred to as a window. While some varicosities have a window only a few tens of nanometres in width, others have more than one window, and some are devoid of Schwann cell altogether, so that their entire axolemma is in contact with the basal lamina. The Schwann cell never extends beyond the axon, whereas very often (and possibly always) the axon extends beyond the Schwann cell. (7) Intervaricose segments vary in length and diameter, the narrowest ones accompanying the more clear-cut varicosities. Some intervaricose segments are as small as 50 nm in diameter, contain a single microtubule and lack a Schwann cell sheath. Others, sheathed by a Schwann cell, contain a single neurofilament or no organelles at all. (8) Specialized contacts between an axon and a muscle cell (neuro-muscular junctions) are abundant and are identified by four features: the axon is a varicosity packed with vesicles; the axolemma is exposed (presence of a window); the distance between the two membranes ranges between 10 and 100 nm, mostly 30–50 nm; and the intercellular gap excludes fibrils, such as collagen, but is occupied by a single basal lamina. Any of these parameters, however, can also occur uncoupled (windows on intervaricose segments; varicosities without a window; exposed axolemma far from a muscle cell). (9) There are no direct contacts between axons. Even when they run close to each other within a bundle, they are always separated by a Schwann cell process. (10) The muscle cell membrane is concave beneath the varicosities; however, the muscle cell ultrastructural features in the region of the neuro-muscular junction are not different from those in other regions of the cell. (11) On average there is more than one neuro-muscular junction per muscle cell, and examples of muscle cells receiving multiple nerve endings from one or from two axons are picked up by the serial sections. (12) A striking feature of the bladder innervation is the variability of its ultrastructural parameters. The bladder innervation does not appear to be built on a rigid structural plan, and the notion of loose-patterned innervation is presented.     

Surgery: Adenomyosis at hysterectomy: a study on frequency distribution and patient characteristics

To evaluate the prevalence and risk factors for adenomyosis,the clinical records of consecutive women undergoing hysterectomyduring a 3 year period were retrieved. Data were collected onindication for the intervention, general sociodemographic characteristicsof the patients, age at menarche, parity, abortions, and menopausalstatus at surgery. Adenomyosis was diagnosed in 332 of the 1334cases (24.9%). The condition was present in 146 of the 627 patients(23.3%) with fibroids and menorrhagia, 68 of the 265 (25.7%)with prolapse, 21 of the 98 (21.4%) with ovarian cysts, 19 ofthe 100 (19%) with cervical cancer, 31 of the 110 (28.2%) withendometrial cancer, 16 of the 57 (28.1%) with ovarian cancer,and 19 of the 77 (24.7%) with miscellaneous indications. Thesedifferences were not statistically significant (x²₆ = 11.14).In comparison with nulliparous women, the odds ratio was 1.3and 1.5 respectively in women with one and two births (x²₁ trend= 5.76, P < 0.05). No relationship was found between ageat surgery, age at menarche, indications for surgery, menopausalstatus at intervention, and presence of endometriosis. Our findingsdo not support the notion that adenomyosis is more frequentlyrelated to particular clinical conditions, and suggest thatparity may be associated with an increased frequency of adenomyosis.     

Isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine-activated killer cells in the treatment of in-transit metastases from limb cutaneous melanoma

Background: Therapies of advanced melanoma patients with interleukin-2 (IL-2) and cytotoxic lymphocytes have produced interesting results, but a larger diffusion of these treatments is limited by the severe side effects due to IL-2 systemic infusion. A strictly regional administration of IL-2 and cells by an isolation perfusion (IP) in extracorporeal circulation (ECC) for the treatment of regional melanoma metastases could improve tolerability and efficacy of this specific modality of immunotherapy. Methods: Ten patients were submitted to adoptive immunotherapy with IL-2 and lymphokine-activated killer (LAK) cells by IP in ECC. The schedule of treatment included the first course of a 5-day systemic administration of IL-2 (Proleukin, EuroCetus 9–12 × 10⁶ IU/M²/day continuous infusion); autologous LAK cells were obtained via leukapheresis and after in vitro activation were given (range 8–28 × 10⁹) along with IL-2 (120-2,400 IU/ml of perfusion priming) to the affected limb by IP; IL-2 (9–12×10⁶ IU/m²/day) was also administered by systemic continuous infusion for 5 days starting on the day after IP. Results: All patients concluded the treatment without any major local or systemic toxicities. Clinical responses included one complete and six partial remissions; three patients had stable disease. All patients are alive. Follow-up after IP ranged from 12 to 35 months (median: 22). The analysis of circulating lymphocytes revealed the rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues. Conclusions: IP with IL-2 and LAK cells is a new approach for the treatment of in-transit metastases due to cutaneous melanoma. The treatment appears to be feasible and reliable. Further biological and immunological studies should permit amelioration of the present modality of treatment.     

Giant abdominopelvic epithelioid angiomyolipoma associated with tuberous sclerosis: Report of a case

(Received for publication on July 16, 1998; accepted on Mar. 11, 1999)     

How Reliable Are Textured Implants Used in Breast Surgery? A Review of 510 Implants

Five hundred ten implants were used in 273 patients. The follow-up was between 3 months and 8 years. Four hundred nineteen prostheses were used for subglandular breast augmentation, 91 for subpectoral breast reconstruction. All the breasts were checked personally: 397 augmented breasts and 86 reconstructed breasts—94.7%. The objective criterion was the Baker classification: grades I and II, good result; and grades III and IV, poor result. Results were as follows: Baker I, 397 breasts; Baker II, 78 breasts (I + II, 98.3%); Baker III, 5 breasts; Baker IV, 3 breasts (III + IV, 1.7%). Three prostheses were removed after 3, 4, and 6 years because the textured surface was totally damaged. Two bilumen prostheses lost the saline fluid. The complication rate due to the implants was very low.     

Prevalence and clinical relevance of Blastocystis hominis in diverse patient cohorts

The pathogenicity of Blastocystis hominis is extensively debated in the medical literature. Therefore, we did a prevalence study to investigate the association between the presence of several intestinal parasites and gastrointestinal symptoms in diverse patient cohorts. The study population consisted of 1216 adults, including immunocompromised patients, institutionalized psychiatric or elder subjects, immigrants from developing countries, travellers to developing tropical countries and controls. Several variables for each risk group were considered. Stools specimens, collected in triplicate, were processed by the same technicians. Clinical data about each subject were provided by standardized questionnaires. The presence of gastrointestinal symptoms were related to the presence of any parasite. In addition, on the basis of microbiological results, five subgroups of subjects were evaluated. The results showed a high prevalence of parasites in all the risk groups. Immunocompromised status, recent arrival from developing countries and the presence of behavioural aberrations were significantly related to presence of parasites. B. hominis was the parasite most frequently detected in each studied group. B. hominis showed a significant correlation with gastrointestinal symptoms only when detected in the group including subjects with a severe immunodepression. Immunodepression seems to be a factor of primary importance of the pathogenic role of B. hominis.     

Increased resting lipid oxidation in Crohn's disease

Resting energy expenditure (REE) was measured by indirect calorimetry and body composition was assessed by both direct (bioimpedance) and indirect (anthropometry) methods in 20 hospitalized patients with biopsy-proven ileal Crohn's disease and in a group of 16 healthy volunteers matched for sex, age, and height with the patient group. The Crohn's disease activity index was below 120 in all patients studied. who were treated with a low dose of corticosteroids (0.2–0.3 mg/kg body wt of prednisone). The average weight of Crohn's patients was signficantly lower than that of controls (55.70 vs 70.50 kg,P<0.001) due to both lower fat mass (9.97 vs 18.30 kg,P<0.001) and lower lean body mass (45.72 vs 52.20 kg,P<0.02). The average REE was significantly higher in the control group (1785.42±7.503 vs 1559.1±48.39 kcal/day,P<0.001). However, these differences disappeared when REE was normalized by lean body mass (LBM) (34.49±2.56 vs 34.704±3.75 kcal/kg LBMP=NS). The nonprotein respiratory quotient was significantly lower in the patient group (0.823±0.031 vs 0.882±0.012.P<0.025), indicating an increased lipid oxidation. This increased lipid oxidation might explain the reduced fat stores found in the group of Crohn's patients, suggesting also that a sufficiently lipid-rich diet could be useful in their nutritional management.     

Managed care in the public mental health system

The movement towards managed care in the public mental health system has surpassed efforts to develop a systematic literature concerning its theory, practice, and outcome. In particular little has been written about potential challenges and difficulties in translating managed care systems from their origins in the private sector to the delivery of public sector mental health services. This paper provides an overview of managed care definitions, organizational arrangements, administrative techniques, and roles and responsibilities using a theoretical framework adopted from economics referred to as principal-agent theory. Consistent with this theory, we assert that the primary function of the managed care organization is to act as agent for the payor and to manage the relationships between payors, providers, and consumers. From this perspective, managed care organizations in the public mental health system will be forced to manage an extremely complex set of relationships between multiple government payors, communities, mental health providers, and consumers. In each relationship, we have identified many challenges for managed care including the complexity of public financing, the vulnerable nature of the population served, and the importance of synchronization between managed care performance and community expectations for the public mental health system. In our view, policy regarding the role of managed care in the public mental health system must evolve from an understanding of the dynamics of government-community-provider-consumer agency relationships.Mary Masland, M.S.P.H., is Research Associate, Institute for Mental Health Services Research.Giorgio Piccagli, Ph.D., is Affiliated Investigator, Institute for Mental Health Service Research.This work was supported by the National Institute of Mental Health funded Center for Research on the Organization and Financing of Care for the Severely Mentally Ill (P50-MH43694).     

Ubiquitinated neurites are associated with preamyloid and cerebral amyloid β deposits in patients with hereditary cerebral hemorrhage with amyloidosis Dutch type

Summary Here ditary cerebral hemorrhage with amyloidosis Dutch type (HCHWA-D) is characterized clinically by recurrent strokes and pathologically by deposition of amyloid (A) in cerebral vessel walls and, to a lesser extent, in the neuropil. Distinct from Alzheimer's disease, amyloid formation in HCHWA-D is not associated with neurofibrillary changes. Since a central issue in the pathophysiology of Alzheimer's disease and related conditions is the role of A in the neurodegencrative process, we investigated HCHWA-D brains for the presence of neuritic abnormalities using antibodies to ubiquitin and to phosphorylated neurofilaments. The study showed that amyloid deposits in the vessel walls and in the neuropil were surrounded by abnormal ubiquitinated neurites, suggesting that A deposition induces neuritic changes.Supported by the Italian Ministry of Health. Department of Social Services, and by N.I.H. Grants AG05891 and AG08721 (to B.F.)     

Early MRI findings in Creutzfeldt-Jakob disease

We describe the MRI changes preceding the onset of myoclonus in two patients whose post-mortem examination confirmed the diagnosis of Creutzfeldt-Jakob disease (CJD). MRI showed changes in the striatum early in the course of CJD (2–6 months after the onset of apathy, interpreted as depression, and 1–2 months before the onset of further clinical symptoms). Only in one patient did electroencephalography record the typical triphasic sharp-waves, 1 month after MRI.