Adenosine A1 receptor activation mediates suppression of (-) bicuculline methiodide-induced seizures in rat prepiriform cortex

The protective effects of a series of stable adenosine analogs against generalized seizures initiated by focal injection of bicuculline methiodide into the rat prepiriform cortex (PPC) were studied by microinjection of these compounds into this brain area. The adenosine agonists, 5'-N-(ethyl)carboxamido-adenosine (NECA), cyclohexyladenosine, cyclopentyadenosine, 2-chloroadenosine and R- and S-phenylisopropyladenosine (R- and S-PIA), protected animals against seizures in a dose-dependent, and extremely potent manner. NECA, the most potent compound evaluated, completely prevented seizures at doses greater than or equal to 6.8 pmol. In contrast, heroic doses of the A2 selective ligand, 2-phenylaminoadenosine, afforded no protection against seizures. The rank order of potency of these compounds in suppressing seizures is as follows: NECA greater than cyclohexyladenosine greater than cyclopentyladenosine greater than or equal to R-PIA greater than 2-chloroadenosine greater than S-PIA much greater than 2-phenylaminoadenosine. These data suggest that the antiseizure activity of these compounds in the PPC results from activation of A1 adenosine receptors. Quantitative autoradiographic analysis of the distribution of tritiated adenosine agonists 30 min after microinjection in the PPC reveals that [3H]NECA diffuses to a significantly greater extent than R-[3H]PIA, which may contribute to the relatively greater potency of the former compound in suppressing bicuculline methiodide-induced seizures. These results suggest that adenosine A1 receptors may participate in the normal inhibitory regulation of the PPC, a forebrain area which may play a significant role in the pathobiology of epilepsy.     

Peter Holland: a pioneer of occupational medicine.

The earliest recorded occupational health service in this country was that established in a cotton spinning factory at Quarry Bank Mill in Cheshire. The mill was built in 1784 by Samuel Greg and his partners. They employed local labour and also some parish apprentices. Happily, Samuel Greg was a good christian and, having created a modern factory and a model village with a church and a school, he was equally concerned for the physical welfare of his employees. Accordingly, he appointed a doctor to make pre-employment examinations of the apprentices and to visit regularly to deal with the health problems of a community of some 400 people. The man he chose was Peter Holland of Sandlebridge, who had served his medical apprenticeship under Dr Charles White of Manchester. The first record of the employment of a doctor was in 1796, but from 1804 to 1845 (doubtless in response to the early factory legislation) each visit of the doctor was entered in a day book with either an indication of fitness to work or details of the treatment required. The complete record consists of two hardback foolscap notebooks that provide a fascinating insight into the medical practice of the times when the industrial revolution was just getting under way. One of the more interesting features is the preservation of medical secrecy. Dr Holland made his comments on the case in shorthand and his instructions in longhand. By a fortunate coincidence the key to the shorthand was discovered and this has now been largely transcribed. Although much of the content of the diaries is the day by day practice of medicine at the time, there are many illuminating glimpses of the early practice of occupational medicine.     

Epidemic dysentery caused by Shigella dysenteriae type 1: a sentinel site surveillance of antimicrobial resistance patterns in Burundi.

Annual epidemics of bacillary dysentery have been a public health problem in Burundi for the last 14 years. Recent civil unrest, resulting in the displacement of large numbers of people into refugee settlements, has aggravated the situation. We report the results of a nationwide, health-centre based, sentinel site survey to check the drug resistance of Shigella dysenteriae type 1 (Sd1), the causal organism of such epidemics. Shigella spp. (of which 97% were Sd1) were isolated from 73% of the 126 specimens collected from six main sites around the country. There was no difference in culture results from fresh and frozen stool specimens. Overall Sd1 resistance to commonly available antibiotics (sulfamethoxazole + trimethoprim, ampicillin, tetracycline, and chloramphenicol) varied from 77% to 99% and was fairly uniformly distributed over the country. All Sd1 isolates were susceptible to newer drugs, such as ciprofloxacin and ceftriaxone. Resistance to nalidixic acid, the current first line of treatment for bacillary dysentery in Burundi, varied from 8% to 83% in the different sentinel sites; global resistance was 57%.     

Gastric accommodation and emptying in evaluation of patients with upper gastrointestinal symptoms.

BACKGROUND & AIMS: Endoscopy-negative dyspepsia is a common symptom that often is difficult to define in pathophysiologic terms. The aim of this study was to assess the frequency of disordered gastric accommodation and emptying in patients referred with unexplained upper gastrointestinal symptoms. METHODS: A computerized diagnostic index was used to identify all patients, 18-70 years old, who underwent single-photon emission computed tomography (SPECT) to assess gastric accommodation at Mayo Clinic Rochester over a 3-year period. Demographics, clinical features, and results of diagnostic testing, including scintigraphic gastric emptying, were extracted from the electronic record. RESULTS: A total of 214 patients were identified; the primary clinical diagnoses were functional dyspepsia, postfundoplication syndromes, rumination syndrome, and diabetic dyspepsia. Gastric accommodation was impaired in 43% of the whole group: 47% of functional dyspepsia, 44% of postfundoplication syndromes, and 33% of diabetic dyspepsia. Delayed gastric emptying was most prevalent in diabetic dyspepsia, and was accelerated in postfundoplication syndromes groups. Thirty-seven percent of patients had abnormal gastric emptying. The highest prevalence of delayed gastric emptying was in the diabetic dyspepsia and accelerated gastric emptying in postfundoplication syndromes groups. Twenty-five percent of patients with normal gastric emptying had impaired accommodation. Upper-gastrointestinal symptoms were not different in groups based on gastric accommodation or emptying results. CONCLUSIONS: Impaired gastric accommodation is common in patients with unexplained dyspepsia. Symptoms alone cannot predict physiologic disturbances. These noninvasive tests identify single or combined pathophysiologic disturbances and may help to identify subgroups of patients as candidates for more selective pharmacotherapy in the future.     

Concurrent ferromagnetic hyperthermia and 125I brachytherapy in a rabbit choroidal melanoma model.

Ferromagnetic (FM) thermoseeds and radioactive (125I) seeds were combined in an episcleral plaque to give concurrent hyperthermia and irradiation for enhanced tumour destruction. A Greene melanoma cell line was utilized to study the interaction between these treatment modalities. We attached five FM thermoseeds (with an operating temperature of 48 degrees C) in parallel with alternating rows of 125I seeds onto the inner surface of each 14 mm Silastic plaque. Plaques were centred over a 3-6 mm (diameter) intraocular melanoma in each rabbit. Some rabbits were then placed within a heating coil, and their eye tumours were warmed rapidly to therapeutic temperatures (43.6 degrees C across the tumour base) while the temperature of normal conjunctiva across the globe did not exceed 38.5 degrees C. Analysis of 49 treated eye melanomas showed 50% local tumour control at 41.7 Gy for 125I alone, whereas only 9.5 Gy were needed to give the same local control rate after 125I with concurrent FM hyperthermia. Thus, a thermal enhancement ratio of 4.4 was obtained. Hyperthermia alone gave a 20% tumour response rate, but responses were only temporary. We conclude that FM thermoseeds can be used to deliver biologically effective hyperthermia concurrently with radiation, thereby reducing the dose of radiation needed for tumour control.     

The lateral chest X-ray: Is it necessary for emergency department patients?

To determine the utility of the lateral view of the chest in emergency department patients, records of all patients who had had 2-view chest x-rays ordered in the emergency department were reviewed retrospectively. A study radiologist recorded a reading of the posteroanterior (PA) radiograph alone. The lateral radiograph was then provided, along with the PA view, and a second reading was recorded. A comparison was then made between the first and second readings.A total of 417 sets of x-rays were included. The PA view alone successfully diagnosed or suspected 92% of pulmonary nodules, 95% of effusions, 97% of cases of emphysema, 98% of pneumonias, and 100% of cases of cardiomegaly, pulmonary edema, interstitial pulmonary disease, and atelectasis.In the emergency department patient population, lateral views of the chest have minimal diagnostic yield and therefore may be used selectively to safely decrease the amount of breast radiation exposure to young women.     

Nephrectomy during operative management of retroperitoneal sarcoma

Background: Complete resection of a retroperitoneal sarcoma often requires removal of adjacent organs. In this study we evaluated the role of nephrectomy during operation for retroperitoneal sarcoma. Methods: Between July 1982 and July 1995, 75 of the 371 (20%) patients who underwent resection of retroperitoneal sarcoma at MSKCC underwent concommitant nephrectomy. Data concerning the reasons for nephrectomy, degree of sarcomatous renal involvement, and survival were retrospectively analyzed. Results: Fifty-four patients (72%) underwent nephrectomy during the initial resection, and 21 (28%) during a resection of a recurrent or persistent tumor. The most common reason for nephrectomy was total encasement by sarcoma (n=40; 53%), followed by dense adherence of the tumor to the kidney (n=21; 28%), and the direct invasion of the kidney by tumor (n=2; 3%). Pathology demonstrated an absence of kidney invasion in the majority of cases (55 of 75; 73%). Renal capsular invasion was present in 11 of 75 (15%), renal parenchymal invasion in 7 of 75 (9%), and renal vein invasion in 2 of 75 (3%) of cases. There were no significant differences in survival based on degree of sarcoma involvement of the kidney, tumor grade, or whether the resection was for primary or recurrent disease. The 53 patients who underwent a complete gross resection of all tumor had a significantly improved long-term survival compared to the 20 patients who did not (50% versus 20% DFS at 5 years, respectively; p<0.001). Conclusions: Decisions for concomitant nephrectomy during resection of retroperitoneal sarcoma should be based on whether this maneuver will provide a complete resection of all gross tumor, in which case the long-term disease-free survival of 50% is comparable to the reported 5-year survival of all patients with retroperitoneal sarcoma who are completely resected. Presented at the 49th Annual Cancer Symposium of the Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

Propofol Increases Contractility during α1a-Adrenoreceptor Activation in Adult Rat Cardiomyocytes

Background: The objective of this study was to identify the extent to which propofol alters intracellular free Ca2+ concentration ([Ca2+]i), myofilament Ca2+ sensitivity, and contraction of individual cardiomyocytes during activation of [alpha]1a adrenoreceptors and to determine the cellular mechanism of action.

Methods: Freshly isolated ventricular myocytes were obtained from adult rat hearts. Myocyte shortening and [Ca2+]i were simultaneously monitored in individual cardiomyocytes exposed to phenylephrine after treatment with chloroethylclonidine ([alpha]1b-adrenoreceptor antagonist) and BMY 7378 ([alpha]1d-adrenoreceptor antagonist). Data are reported as mean +/- SD.

Results: Phenylephrine increased myocyte shortening by 124 +/- 9% (P = 0.002), whereas peak [Ca2+]i only increased by 8 +/- 3% (P = 0.110). Inhibition of phospholipase A2 and phospholipase C attenuated the phenylephrine-induced increase in shortening by 84 +/- 11% (P = 0.004) and 15 +/- 6% (P = 0.010), respectively. Inhibition of protein kinase C (PKC) and Rho kinase attenuated the phenylephrine-induced increase in shortening by 17 +/- 8% (P = 0.010) and 74 +/- 13% (P = 0.006), respectively. In the presence of phenylephrine, propofol increased shortening by 40 +/- 6% (P = 0.002), with no concomitant increase in [Ca2+]i. PKC inhibition prevented the propofol-induced increase in shortening. Selective inhibition of PKC[alpha], PKC[delta], PKC[varepsilon], and PKC[zeta] reduced the propofol-induced increase in shortening by 12 +/- 5% (P = 0.011), 36 +/- 8% (P = 0.001), 32 +/- 9% (P = 0.007), and 19 +/- 5% (P = 0.008), respectively. Na+-H+ exchange inhibition reduced the propofol-induced increase in shortening by 56 +/- 7% (P = 0.001).