Experimental transmission of Plasmodium mexicanum by bites of infected Lutzomyia vexator (Diptera: Psychodidae)

Lutzomyia vexator is an efficient experimental vector of Plasmodium mexicanum, infecting 69.2% (9/13) of the Sceloporus undulatus lizards with as few as one bite. Sporozoites were present in the salivary glands by day 6.5 postfeed and infective by day 8 postfeed at 27 degrees C. The prepatent period was relatively long, ranging from 23 to 40 days for bite-induced infections and appears to be related to the number of sporozoites injected. The acute phase of the infection is initially exponential and rapid. All lizards (6) that were not sacrificed, died of fulminating infections from 13 to 56 days after parasites were seen in the blood films. Gametocytes from 2 experimentally infected lizards were infective to L. vexator during the course of the acute infection. The majority of P. mexicanum parasites were in erythrocytes of Sc. undulatus. Exoerythrocytic forms were observed in circulating lymphocytes and thrombocytes, lymphocytes of spleen and bone marrow, and endothelial cells of brain capillaries.     

Multiple medication: problems of the elderly patient.

Elderly persons are apt to receive multiple drugs for many diseases. Prescribers should take extra care in persons aged over 65-70 years, and especially the very old. The main problem of the elderly is the unpredictability of their response to drugs. Self-medication with both prescribed and over-the-counter drugs worsens this problem. Drug actions may be altered by impairment of the liver, kidneys and brain, or acute illness, or both. Unwanted (adverse) drug reactions often produce rapid and unduly severe illness in the old. Some antibacterial antibiotics like the sulphonamides are best avoided. Taking many drugs together promotes adverse interactions between the drugs. Drugs with a narrow therapeutic ratio, such as warfarin, digoxin, the aminoglycosides, and many antiarrhythmic drugs, cause clinical problems. Old persons respond more abruptly to drugs like benzodiazepines, opioid analgesics, and antiparkinsonian drugs. Anaesthesia given on top of psychotropic drugs may damage the central nervous system. The elderly brain is more sensitive to induction agents and short-acting intravenous anaesthetics, like alfentanil and midazolam; the elderly liver is more easily damaged by inhalational anaesthetics like halothane. The overall benefit:risk ratio should be judged for every drug in each patient. Wherever possible, drug treatment should be avoided. If drugs are given, safe drugs with broad therapeutic ratios and tissue- or receptor-specific actions are preferable. Drug doses are usually, but not always, reduced. Benefit from a drug should be assessed early. Severe unpredictable adverse reactions need immediate cessation of the drug and prompt patient support. The practitioner should frequently review the patient's continuing need for drugs.     

Management of chronic lunotriquetral ligament tears

Treatment of chronic disruptions of the lunotriquetral (LT) ligament is not well-defined. Eleven patients treated by LT fusion with use of a compression screw are reported. The injury frequently resulted from hyperextension of the wrist. Pain on the ulnar side of the wrist, limited motion, and tenderness over the LT joint exacerbated by ballottement were present. Standard radiographs were normal. Arthrography showed the ligamentous tear in all cases. After operation, immobilization was continued until fusion was apparent radiographically. Fusion was achieved in all cases between 2 and 5 months. Four patients were free of pain, four patients had pain only at the extremes of motion, and three patients had persistent pain. Mean wrist motion was as follows (preoperative/postoperative): flexion (53 degrees/45 degrees), extension (60 degrees/49 degrees), radial deviation (17 degrees/21 degrees), and ulnar deviation (25 degrees/18 degrees). Maximum grip strength as a percentage of the uninjured side was 73% preoperatively and 59% postoperatively. LT tears can exist de novo or as part of the ulnar impaction syndrome; a method for differentiation is presented.     

Early effects of tetraethylammonium chloride on the contractile properties of isolated rabbit basilar arteries

The acute vascular effects of tetraethylammonium chloride (TEA) were examined on annular segments of rabbit basilar arteries. Contractions induced by the potassium channel blocker were compared with those obtained for potassium chloride, 5-hydroxytryptamine (5-HT) and norepinephrine (NE). The greater magnitude of the contractions was of the following order: [K+] greater than 5-HT greater than TEA greater than NE. High concentrations of TEA alone (10(-2) M) generated spontaneous oscillatory contractions in cerebral vessels that were normally quiescent. Low concentrations of TEA (10(-8)-10(-6) M), which had no vasomotor properties per se, enhanced the contractile response of submaximal concentrations of 5-HT (10(-7) M) and NE (3 X 10(-6) M) and attenuated the contraction produced by 60 mM [K+]. An increased vascular response to the amines was still evident up to 3 h after the addition of TEA despite frequent rinsing with fresh buffer solutions. On arteries precontracted with TEA (10(-2) M), but not high [K+], the subsequent addition of 5-HT (10(-7) M) still induced a powerful constriction. Repeated concentration-response curves for [K+] were reproducible and, in the presence of TEA (10(-8) or 10(-6) M), the curve was displaced to the right in a competitive manner. A higher concentration of TEA (10(-4) M) was devoid of any blocking properties on the [K+]-induced response whereas, at 10(-3) M TEA, the response was potentiated, as evidenced by a shift of the curve to the left. Interactions between TEA and the cumulative response to 5-HT were difficult to interpret. Repeated exposures of the artery to 5-HT resulted in an increased maximal response with each determination (EAm = 127 +/- 9% and 149 +/- 14% of control values following the second and third applications, respectively). With TEA (10(-6) M), the increase in the maximal contractile effect noted previously was not observed. Contractions induced by single concentrations of TEA (10(-2) M) or [K+] (60 mM) were calcium dependent, were abolished completely in a calcium-free medium, and were depressed by the calcium antagonist nimodipine. 5-Hydroxytryptamine-induced contractions (10(-5) M) were less sensitive to withdrawal of calcium from the extracellular medium (31 +/- 6% relative to the maximal response at 4 mM calcium). Hence, an acute reduction in potassium conductance in cerebrovascular smooth muscle produced by TEA has complex, concentration-dependent effects and reproduces only part of the spectrum of effects of cisternal injection of blood on cerebrovascular reactivity.     

Enhancement of hepatic hemangiomas with levovist on coded harmonic angiographic ultrasonography.

OBJECTIVE: To evaluate the pattern of contrast enhancement with Levovist on coded harmonic angiographic ultrasonography of hepatic hemangiomas. METHODS: Twenty hemangiomas were evaluated with coded harmonic angiographic ultrasonography and a microbubble contrast agent. Verification of the diagnosis of a hemangioma was made by means of dynamic computed tomography (n = 8), dynamic magnetic resonance imaging (n = 1), radionuclide scanning (n = 6), or follow-up ultrasonography (n = 5). Ultrasonographic images were obtained before contrast agent administration and with a bolus injection of 2.5 g of a microbubble contrast agent (300 mg/mL Levovist; Schering AG, Berlin, Germany) every 10 to 15 seconds for 5 minutes. The contrast enhancement patterns of the 20 hemangiomas were assessed. RESULTS: The tumor diameters as measured on ultrasonography were 7 to 97 mm (mean, 26.7 mm). Of the 20 hemangiomas, peripheral globular enhancement with progressive centripetal fill-in was shown in 15 (75%), rimlike enhancement with progressive centripetal fill-in was shown in 2 (10%), and homogeneous enhancement was shown in 1 (5%). In the remaining 2 lesions (10%), the enhancement patterns could not be seen, because they were not found on coded harmonic angiographic ultrasonography. CONCLUSIONS: Coded harmonic angiographic ultrasonography with a microbubble contrast agent can depict the typical enhancement pattern in most hepatic hemangiomas.     

Effect of cisplatin chemotherapy on extracortical tissue formation in canine diaphyseal segmental replacement

The reconstruction of large bone and joint defects after the resection of malignant tumors remains a major challenge. Chemotherapy has significantly lowered the risk of metastasic disease, but complications associated with reconstructive techniques continue to result in late morbidity. In the present study, biomechanical torsion testing, gait analysis, and histomorphometric and scanning electron microscopic evaluations of 24 dogs were used to examine the effects of preoperative and postoperative administration of cisplatin on the biologic fixation of a porous-coated segmental replacement prosthesis. The chemotherapy consisted of four cycles of cisplatin administered at a dosage of 75 mg/m:² preoperatively or postoperatively. The healing was enhanced by use of an autogenous corticocancellous bone graft. The graft was placed evenly around the prosthesis and the adjacent femoral cortex. Mechanical analyses of torsional stiffness, yield strength, and maximum strength revealed no statistically significant differences between the groups at 12 weeks. Such lack of difference was mainly due to the penetration of highly organized fibrous tissue into the porous surface; this provided strong fixation of the implant to bone even in the absence of bone ingrowth. Although bone ingrowth into the prostheses was not affected, electron microscopic, histomorphometric, and radiologic analyses showed a clear difference in the formation of new bone around the prosthesis. Preoperative chemotherapy did not alter the formation of new bone, but specimens from animals treated postoperatively with cisplatin showed significantly less bone graft resorption and less new bone formation. Hence, the effect of cisplatin administration caused only a temporary delay, not a permanent effect, on extracortical capsule formation. The formation of extracortical bone and soft tissue might prevent debris-incised osteolysis and, therefore, prevent late complications by forming a tight capsule around the bone-prosthetic interface.     

Alterations in the superoxide dismutase gene of an isoniazid-resistant strain of Mycobacterium tuberculosis.

Genetic analysis of a set of six Mycobacterium tuberculosis strains differing in virulence for the guinea pig revealed an altered restriction enzyme fragmentation pattern associated with the superoxide dismutase (SOD) gene in a low-virulence, isoniazid-resistant strain. In addition, it was found that the SOD enzyme produced by the isoniazid-resistant strain differed in its electrophoretic mobility from the SOD of other M. tuberculosis strains. Detailed analysis of these strain-specific differences showed that the restriction fragment length polymorphism resulted from the presence of a copy of a repetitive element 552 bp upstream of the SOD gene and that the anomalous electrophoretic mobility arose from a single nucleotide change, resulting in replacement of an aspartic acid residue by histidine in the SOD enzyme of the isoniazid-resistant strain. Possible relationships between genetic changes and strain-dependent differences in virulence are discussed.