Pathophysiology of experimental leishmaniasis: the role of parasite physiology in the development of metastatic disease

This paper addresses the issue of how physiological properties of Leishmania determine the pattern of development of disseminated leishmaniasis in the mammalian host. It presents direct experimental evidence from in vivo studies that species of Leishmania differ in their capacity to multiply in cutaneous and visceral sites which results in differences in the pattern and rate of development of leishmaniasis. It was found that Leishmania mexicana amazonensis begins to multiply in the cutaneous site of inoculation within 7 days. Parasites, detected in the liver and spleen at 4 weeks, increased 100-fold during the next 4 months. However, the slow multiplication of L. mexicana amazonensis in the liver and spleen was more apparent than real. Parasites implanted in those organs of athymic nude mice by an intravenous injection were rapidly eliminated with a half-time of 16 hr. Thus, the parasites found in small numbers in the liver during the development of disseminated cutaneous disease in mice are most likely those which have been recently removed from the blood. Those few parasites that are not removed from the blood can establish metastatic foci in distant cutaneous sites, and replicate progressively once there.     

A prospective randomized trial of laparoscopic versus open appendectomy.

BACKGROUND. Laparoscopic appendectomy is feasible, but whether it confers any advantage to patients with acute appendicitis is not known. We performed a randomized controlled trial to compare results of laparoscopic and open appendectomy in patients with signs and symptoms suggesting acute appendicitis who were seen by one surgical team. METHODS. Sixty-two consecutive patients were randomized, 30 to laparoscopy and 32 to a classical open appendectomy. Postoperative recovery, complications, and return to normal activities were compared in the two groups. RESULTS. The laparoscopy group were discharged earlier (2.5 vs 3.8 days, p less than 0.01). Postoperative complications were more frequent after open appendectomy. Follow-up showed less pain, shorter bed stay at home, and faster return to work and sport after laparoscopic appendectomy. CONCLUSIONS. This prospective randomized study shows that laparoscopic appendectomy is superior to open appendectomy in terms of hospital stay, postoperative complications, and return to normal activities and is recommended as the approach of choice in the management of acute appendicitis.     

A monoclonal antibody to a parasympathetic neurotrophic factor causes immunoparasympathectomy in mice

A monoclonal antibody capable of blocking the biological activity of the ciliary neurotrophic factor purified from bovine cardiac muscle has been produced. This antibody, when administered perinatally to mice, causes a failure of the normal development of the parasympathetic innervation of the iris as determined by assay for the activity of the cholinergic marker enzyme choline acetyltransferase. The same treatment has no effect on the adrenergic neuronal marker, tyrosine hydroxylase. This immunoparasympathectomy suggests that the ciliary neurotrophic factor has an essential role in regulating the development of the mammalian parasympathetic nervous system.     

Long-term risk of second malignant neoplasm after a cancer in childhood

The risk of subsequent second malignant neoplasm was studied in a cohort of 634 patients, treated for a childhood cancer at the Gustave Roussy Institute between 1942 and 1969, and in complete remission five years after diagnosis. The most frequent types of first primary cancers (FPC) were Wilms' tumours (28% of the children), neuroblastomas (16%), lymphomas (12%) and soft tissue sarcomas (11%). Median follow-up duration after FPC was 19 years. Thirty-two patients (obs = 32) developed a total of 35 second cancers. Bone, thyroid, connective tissues and skin were the most frequent types of second cancer, with six patients for each type. The average annual incidence of second cancer was 0.36%. The average annual incidence for the periods 5-9, 10-14, 15-19, 20-24 and 25+ years after FPC was respectively 0.16%, 0.34%, 0.36%, 0.71% and 1.18%. The cumulative incidence of second cancer for the periods 5-20, 5-25 and 5-30 years after FPC was, respectively, 4.3% (95% CI: 2.8-6.6%), 7.8% (95% CI: 5.1-11.8%) and 13.0% (95% CI: 8.2-20.0%). The expected number of cancers in the cohort, computed from Danish cancer incidence data, was exp = 2.2. When compared to this expected number, the average annual excess incidence of second cancer, defined as obs-exp divided by the number of person years of observation, was 0.33%. This rose from 0.15% for the period 5-9 years after FPC to 1.09% for the period beginning 25 years after FPC. The standardised incidence ratio of second cancer (i.e. obs/exp) was 15 (95% CI: 10-21), and was fairly constant in the period extending from 15 to 20 years after FPC diagnosis. Obs/exp was equal to 25 for the patients who had had chemotherapy and equal to 9 for those who had not. Cyclophosphamide seemed less carcinogenic than the other alkylating agents. Obs/exp was similar for the patients who had received radiotherapy and for those who had not. The risk of cancer increased with age in the reference population and increased faster in the cohort, because the standardised incidence ratio is constant over a long period.     

THE ACCEPTANCE OF COMPUTER ASSISTED LEARNING BY MEDICAL STUDENTS

The use of computer assisted learning (CAL) in the medical undergraduate curriculum is increasing. Little is known regarding the acceptability of CAL among medical students. The present study was conducted to investigate the possible anxiety generated by and the acceptability of CAL among medical students. One hundred and twenty-six students completed a questionnaire after using n software package which has been written as an adjunct in teaching urology. The present study demonstrates that there was little anxiety experienced by the students when using CAL and furthermore that there was a high level of acceptance for this type of instruction. This is encouraging for medical educators involved in producing multimedia packages for teaching medicine and surgery.     

Acute Oxalate Nephropathy: A New Etiology for Acute Renal Failure Following Nonrenal Solid Organ Transplantation

Acute renal insufficiency (ARI) is a frequent complication of nonrenal solid organ transplantation and may be responsible for an unfavorable outcome, particularly if dialysis is required. The etiology of post-transplantation ARI is poorly understood, with only isolated clinical cases being reported, most imputed to drug toxicity. We report here, the first three observations of irreversible ARI associated with acute oxalate nephropathy (AON) in the course of nonrenal organ transplants: a lung transplant and a lung-liver transplant in two patients with mucoviscidosis, and a cardiac transplant. The diagnosis of AON was made histologically. In all three cases, the ARI supervened after prolonged consumption of antibiotics capable of interfering with the colonic flora, and leading to enteric hyperoxaluria. The recognition of AON as a cause of post-transplantation, ARI underlines hyperoxaluria and digestive hyperabsorption of oxalate as specific risk factors for AON and should permit better posttransplant care of these patients.     

Postamputation Pain and Sensory Changes in Treatment-naive Patients: Characteristics and Responses to Treatment with Tramadol, Amitriptyline, and Placebo

Background: Pain after amputation is common but difficult to treat, and few controlled treatment studies exist.

Methods: In the current study, 94 treatment-naive posttraumatic limb amputees with phantom pain (intensity: mean visual analog scale score [0-100], 40 [95% confidence interval, 38-41]) were randomly assigned to receive individually titrated doses of tramadol, placebo (double-blind comparison), or amitriptyline (open comparison) for 1 month. Nonresponders were crossed over to the alternative active treatment.

Results: After 1 month, phantom pain intensity was 1 (0-2) in the 48 tramadol responders (mean dose, 448 mg [95% confidence interval, 391-505 mg]), 0 (0-0) in the 40 amitriptyline responders (55 [50-59] mg), and 0 (0-0) in the 2 placebo responders, with similar effects on stump pain. Cytochrome P-450 2D6 slow metabolizers derived greater analgesia from tramadol and less from amitriptyline compared with fast metabolizers in the first treatment week (P < 0.01). Electrical pain thresholds increased and pain during suprathreshold stimulation decreased markedly on the stump and, to a lesser extent, on the contralateral limb after 1 month of treatment with amitriptyline or tramadol. Adverse effects were minor in all groups, but more common with tramadol.     

Whole-heart cine MRI using real-time respiratory self-gating.

Two-dimensional (2D) breath-hold cine MRI is used to assess cardiac anatomy and function. However, this technique requires cooperation from the patient, and in some cases the scan planning is complicated. Isotropic nonangulated three-dimensional (3D) cardiac MR can overcome some of these problems because it requires minimal planning and can be reformatted in any plane. However, current methods, even those that use undersampling techniques, involve breath-holding for periods that are too long for many patients. Free-breathing respiratory gating sequences represent a possible solution for realizing 3D cine imaging. A real-time respiratory self-gating technique for whole-heart cine MRI is presented. The technique enables assessment of cardiac anatomy and function with minimum planning or patient cooperation. Nonangulated isotropic 3D data were acquired from five healthy volunteers and then reformatted into 2D clinical views. The respiratory self-gating technique is shown to improve image quality in free-breathing scanning. In addition, ventricular volumetric data obtained using the 3D approach were comparable to those acquired with the conventional multislice 2D approach.     

Online access to NDT for developing countries

As editors we want as many people to have access to NDT as possible.The last 18 months have seen a number of experimental initiativesto test the technical and logistical