The effects of prolonged betahistine administration were studied in institutionalized geriatric patients with particularly severe and long-standing arteriosclerotic dementia. Thirty received betahistine hydrochloride (SERC) or placebo orally in fixed dosage for six months on a double-blind basis and were followed by ward behavioral and psychometric ratings. Six others received active medication and were additionally followed by intracranial rheoencephalography (IREG). Thirty patients successfully completed the two studies. No adverse effects ascribable to the drug were encountered. The results show that betahistine caused definite, strong, and highly significant cerebral and scalp arterial vasodilation and circulatory improvement and that these caused equally definite, strong, and highly significant global improvement in the patients' dementias. Bethahistine, thus, acts in humans as a potent and efficacious cerebral and peripheral microcirculatory and arterial vasodilator which can significantly improve cerebrovascular insufficiency and any associated dementia, no matter how severe either may be and despite the possible presence of large-vessel disease. These improvements sometimes were detected within two weeks or less, developed rapidly to maxima by about 90 days, and were sustained quite well there-after by continued therapy, They may, however, be drug dependent as they regressed in two patients following withdrawal. Various mechanisms whereby a microcirculatory vasodilator can cause arterial vasodilation are considered. The evidence apparently favors that prolonged microcirculatory vasodilatation can cause secondary passive arterial responses. The possibility that the IREG contains external carotid contamination is again examined. Significant discrepancies between the scalp and IREG effects of bethahistine indicate, however, that the response of any such component was negligible within experimental error and that the component, itself, must have comprised but a small percentage of the IREG. Since the circulatory responses detected by the IREG thus arose essentially completely from the effects of betahistine on the cerebral circulation alone, this appears to be the first direct demonstration that cerebral circulatory improvement can cause improvement in mental function in patients with even severe, longstanding, and apparently clinically irreversible arteriosclerotic dementia and that such improvements can be effected pharmacologically.

Aged↗

PubMedDate not supplied

A comparative analysis of radiological and surgical placement of central venous catheters.

PURPOSE: To compare the differences in practice and outcome of all radiologically and surgically placed central venous catheters retrospectively over a 2-year period simultaneously, at a single institution. METHODS: A total of 253 Hickman catheters were inserted in 209 patients; 120 were placed radiologically in 102 patients and 133 were placed surgically in 107 patients. The indication was chemotherapy in 76% of radiological and in 47% of surgical cases; the remainder were for total parenteral nutrition and venous access. RESULTS: There were 6 (4.5%) primary surgical failures and a further 17 (13%) surgical cases requiring multiple placement attempts. Pneumothorax occurred once (0.8%) surgically and four times (3.3%) radiologically. There were no radiological primary misplacements but there were five (3.7%) surgical ones. Catheter or central vein thrombosis occurred in four (3.3%) radiological and five (3.7%) surgical cases. The rate of infection per 1000 catheter-days was 1.9 in radiologically placed catheters and 4.0 in surgically placed ones (p < 0.001). Average catheter life-span was similar for the two placement methods (100 +/- 23 days). CONCLUSION: Radiological placement is consistently more reliable than surgical placement. There are fewer placement complications and fewer catheter infections overall.

Antineoplastic Agents↗

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Hydatidiform mole: an ultrastructural analysis of syncytiotrophoblast surface organization.

The scanning ultrastructural examination of a series of 31 hydatidiform mole and 12 healthy placental specimens of similar gestational age has revealed a variety of surface architectures more common in molar tissue. Characteristic paddle-shaped sprouts, ridging of the syncytial maternal oriented surface and microgibbosities are described. These structures are explicable in terms of organellar hyperplasia of cortical cytoskeletal elements found in healthy tissue. Specific morphological evidence of involvement of these elements in a condition where aberrant growth control leads to the characteristic trophoblastic hyperplasia is a further indication that cytoskeletal elements may mediate transformation. An increase in resolution obtained over previous scanning electron microscope studies has allowed the description of detailed features such as 'caveolar collars' on the maternal oriented healthy and molar trophoblast surfaces. These observations are of relevance to understanding the mechanisms of several cell physiological processes, including transepithelial transport. New observations of a reticular organization in the surface layer of molar trophoblast indicate that a syncytioskeletal layer, with organization resembling that previously described in healthy chorionic villi, is also present in molar villi.

Chorionic Villi↗

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The ntr genes of Escherichia coli activate the hut and nif operons of Klebsiella pneumoniae.

Regulation of the synthesis of glutamine synthetase and of the arginine and glutamine transport systems (Ntr phenotype) in Salmonella have been shown to require two regulatory genes on the C-terminal side of the glnA gene (McFarland et al., 1981). We have cloned a HindIII-EcoRI DNA fragment from Escherichia coli coding for analogous properties with respect to the Ntr phenotype in E. coli. A plasmid containing this E. coli DNA fragment joined to another fragment carrying a cyanobacterial glnA gene (but no functional regulatory genes) was introduced into a Klebsiella pneumoniae mutant with a Gln-Ntr- phenotype, i.e., which could not derepress nitrogenase. The cyanobacterial gene made the Klebsiella strain Gln+ and the E. coli DNA fragment made the strain Ntr+, including the ability to derepress nitrogenase fully. Thus the products of the glnA-linked ntr genes of E. coli can regulate expression of the Ntr-dependent genes of Klebsiella.

Arginine↗

PubMedDate not supplied

Monitoring of CMV infection after renal transplantation: serology, culture, and viral DNA detection by hybrid capture.

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Antibodies, Viral↗

PubMedDate not supplied

Immunogold confirmation that utrophin is localized to the normal position of dystrophin in dystrophin-negative transgenic mouse muscle.

It has been shown previously that when utrophin is highly expressed in mice which lack dystrophin, the muscle pathology is prevented. Immunohistochemical evidence strongly suggests that utrophin in these transgenic mice occupies the position normally filled by dystrophin, although it is not possible to establish this firmly at the level of the light microscope. Using the higher resolution provided by the electron microscope, we demonstrate here by immunogold labelling with both monoclonal and polyclonal antibodies that utrophin, in both its truncated and full-length forms, is indeed specifically located in the subcellular position usually occupied by dystrophin in normal muscle. Moreover, when double-labelling of utrophin and beta-dystroglycan was carried out, colocalisation of the two labels was often seen, indicating an association of the two proteins. Furthermore, when both utrophin and dystrophin were labelled in a transgenic line in which both were simultaneously expressed, the sites of both proteins were in the same zone in relation to the plasma membrane. When both proteins were present, the density of labelling of each was reduced compared with when they are expressed individually, suggesting that there is a finite number of binding sites. These results constitute further support for the view that utrophin might be therapeutically substituted for dystrophin in dystrophic muscle.

Animals↗

PubMedDate not supplied

Relation between FIGO stage, primary tumor volume, and presence of lymph node metastases in cervical cancer patients referred for radiotherapy.

The aims of this study were to determine, firstly, the relationship between FIGO stage and various tumor parameters determined by magnetic resonance imaging (MRI), and, secondly, whether any of these parameters were predictors of lymph node metastases as determined by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) in cervical cancer patients referred for radiotherapy. In 70 consecutive patients, both PET and MRI visualized all primary tumors except for one previously removed by cone biopsy. While clinical diameter and MRI-derived diameter showed a significant relationship between these two measurements (r = 0.70; P < 0.001) there was a large variability in MRI diameter for each FIGO stage and wide overlap. The average volume of primary cervical tumor on MRI was 60 cc (5-256). In FIGO stages, I, II, III and IV, uterine body involvement was present in 58%, 73%, 88%, and 100% of 19, 30, 16, and 5 patients, respectively (Ptrend= 0.015). Node positivity on FDG PET was present in 11% of patients without uterine body extension, but increased to 75% in those with uterine involvement. Average tumor volume in node-negative patients was 49 cc (5-186). Average tumor volume in node-positive patients was 69 cc (8-256). There was a significant association between nodal involvement and both FIGO stage (P = 0.018) and uterine body involvement (P < 0.001), but tumor volume and longitudinal MRI diameter were not statistically significant in unifactor predictors of nodal involvement. In multivariate analysis only uterine body extension, however, was independently related to the risk of nodal involvement. In conclusion, MRI provides noninvasive tumor size evaluation and can also demonstrate invasion of the uterine body that appears to be associated with an increased risk of nodal metastasis. This may provide clinically important prognostic information not available from current FIGO staging.

Adenocarcinoma↗

PubMedDate not supplied

Extravillus endovascular implantation site trophoblast invasion is abnormal in complete versus partial molar pregnancies.

This study examines endovascular trophoblast invasion in pregnancies complicated by complete hydatidiform mole (CM), partial hydatidiform mole (PM) and non-molar abortions (HA). Two hundred consecutive cases from a supra-regional referral centre for suspected trophoblastic disease were examined histologically with particular regard to the presence or absence of endovascular trophoblast invasion of decidual vessels. There were 57 CM, 75 PM and 68 HA. The prevalence of normal endovascular invasion of decidual vessels was significantly lower in CM compared to all other clinical groups, amongst which there were no significant differences. Endovascular trophoblast was identified in about 80 per cent of HA and PM moles, compared to only around 25 per cent of CM (Z = -4.0, P< 0.0001). The majority of cases of complete mole demonstrated a similar appearance, of implantation site showing florid interstitial extravascular trophoblast invasion with surrounding of decidual vessels but without normal endovascular trophoblast invasion or 'plugging' seen. In many cases, there also appeared to be destruction of decidual vessels with interstitial haemorrhage and extensive fresh blood clot present in the histological sections. These findings may provide some explanation regarding the mechanism of clinical findings in molar pregnancy.

Decidua↗

PubMedDate not supplied

Outcome study of minors after parental refusal of paramedic transport.

OBJECTIVE: Patient refusal of paramedic transport against medical advice (AMA) has significant medical-legal implications. Previous studies have investigated patient outcomes after refusal of transport, but none has focused on these events in minors. This study was performed to evaluate the outcomes of this patient population after refusal of transport as well as the significance of base hospital physician discussion with parents in the decision to refuse transport. METHODS: This was a retrospective telephone follow-up survey involving parents of minors for whom transport was refused after accessing emergency medical services (EMS) via the 911 system. Data were initially obtained from paramedic run records and each family was subsequently contacted by telephone and surveyed with regard to their experiences with the field medics in addition to the medical follow-up sought for their child and patient outcomes. RESULTS: Eighty-nine patients met criteria for survey. Telephone contact was made with 44 parents, of whom 32 (73% of those contacted, 36% overall) participated. Twenty-seven (84%) received medical follow-up, either at an emergency department or in a private physician's office. Most patients (89%) who were evaluated and/or treated by a physician were subsequently released, while three children were admitted to the hospital, all three with respiratory or cardiac chief complaints. CONCLUSIONS: Children whose parents refused EMS transport received medical follow-up in the majority of cases, with a small group requiring admission.

Adolescent↗

PubMedDate not supplied

Angular deformity of the lower extremity in children with renal osteodystrophy.

We have treated 15 children with end-stage renal disease (ESRD), renal osteodystrophy, and genu valgum in the last 22 years. In a retrospective review, we determined that periods of metabolic instability, best characterized as an alkaline phosphatase of 500 U for at least 10 months, were associated with progression of deformity. Histomorphometric bone biopsy provided information that proved essential for effective evaluation and treatment in this group. Complications of corrective osteotomy were related to perioperative metabolic instability. A surgical treatment protocol is described, emphasizing preoperative assessment by histomorphometric bone biopsy and multimodal medical management to maintain metabolic stability perioperatively.

Adolescent↗

PubMedDate not supplied

Significance of tumor volume and corpus uteri invasion in cervical cancer patients treated by radiotherapy.

The purpose of this study was to show that in advanced cervical cancer patients treated with curative intent, tumor volume and uterine involvement have independent prognostic value. Eligible patients were those seen at the Peter MacCallum Cancer Centre between December 1995 and June 2001, newly diagnosed with a histologic diagnosis of squamous cell carcinoma or adenocarcinoma of the cervix, FIGO-staged IB-IVA, and having undergone magnetic resonance imaging (MRI) and treated with curative intent. Potential prognostic factors considered were FIGO stage, clinical tumor diameter, histology, age, tumor volume, and corpus invasion status. MRI was used to determine the tumor volume and whether there was invasion of tumor into the corpus uteri. One hundred and seventy-nine patients were eligible for this study. The cut-off date for follow-up was October 2003, one patient was lost to follow-up, and the mean potential follow-up time was 4.5 years (range 0.2-7.7 years). There were 60 (34%), 78 (44%), 34 (19%), and 7 (4%) patients in FIGO stages IB, II, III, and IVA, respectively. The tumors of 107 (60%) patients exhibited corpus invasion. The median tumor volume was 33 mL (range 0.1-200 mL). The four factors, FIGO stage, clinical tumor diameter, corpus invasion, and tumor volume, were all strongly positively correlated (P < 0.001 in each case). The 5-year overall survival (OS) rate for all patients was 55% (standard error = 4%). Of the six factors examined, FIGO stage (P= 0.006), clinical tumor diameter (P= 0.013), corpus invasion (P < 0.001), and tumor volume (P < 0.001) were statistically significantly related to OS duration in unifactor analyses. However, only corpus invasion (P= 0.013) and tumor volume (P= 0.004) were significantly and independently associated with OS in multifactor analyses. In particular, after adjusting for corpus involvement and tumor volume, there was no evidence for any relationship between OS and either FIGO stage (P= 0.49) or clinical tumor diameter (P= 0.58). The results from the analysis of failure-free survival were very similar. We conclude that in patients with advanced cervical cancer, tumor volume and corpus invasion provide important prognostic information over and above that provided by FIGO stage, clinical tumor diameter, histology, and age.

Adenocarcinoma↗

PubMedDate not supplied

Suprascapular neuropathy in pitchers.

The clinical features and preoperative and postoperative electrodiagnostic studies were reviewed in two professional pitchers with a suprascapular neuropathy. These studies demonstrate that denervation of the infraspinatus and/or supraspinatus muscle is not always due to entrapment of the nerve at the suprascapular or spinoglenoid notches, as is often proposed. Similar studies in healthy pitchers during spring training and again at midseason demonstrate that slowing of suprascapular nerve conduction is detectable in some cases as the season progresses. Sagittal sections of a cadaver with the arm fixed in the acceleration phase of the pitching motion demonstrate five possible sites of trauma to the suprascapular nerve. Mechanisms proposed to explain these progressive, but potentially reversible, changes include consideration of biomechanical factors as well as anatomical features. An alternative hypothesis to nerve trauma that explains this symptom complex is intimal damage to the axillary or suprascapular artery and subsequent production of microemboli which become trapped in the suprascapular nerve vasa nervorum.

Adult↗

PubMedDate not supplied

The role of men in nursing.

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Humans↗