Who should determine competence?
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Biomedical subjects
Publications and source records attributed to G Watt.
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Data are presented on the sensitivity, specificity, and positive predictivity of the Hemoccult test based on the experience of the Minnesota Colon Cancer Control Study, a randomized clinical trial to determine whether the use of the Hemoccult test can reduce mortality from colorectal cancer. Rehydrating the slides with a drop of water before processing resulted in an increase in positivity (2.4% to 9.8%), and sensitivity (80.8% to 92.2%) but a decrease in specificity (97.7% to 90.4%) and positive predictivity (5.6% to 2.2%). The effects of age and sex were also evaluated. The test was less specific for men than women (p = 0.03). Specificity was highest for those less than 60 yr of age and decreased with increasing age (p = 0.05). The positive predictivity increased with age from 1.6% for those under 60 yr to 3.6% for those over 70 yr (p = 0.0004).
A fatal case of tuberculous meningitis caused by a multiply-resistant tubercle bacillus is described, the first such case from Southeast Asia. Increased efforts to isolate Mycobacterium tuberculosis from the cerebrospinal fluid and determine the extent and pattern of drug resistance are necessary if the high mortality from this disease is to be reduced.
A mass strategy for the prevention of high blood pressure and its complications is likely to be more effective than high-risk strategies for several reasons: there is no practicable way of identifying in advance a large proportion of future hypertensives; a minority of hypertensive complications occur in individuals with pressures high enough to warrant treatment; and treatment has little or no effect on the incidence of the major hypertensive complication, coronary heart attacks. The effect of a broad-based dietary prevention programme is not proven, but such a strategy offers a reasonable prospect of a broad range of benefits, and is likely to prove acceptable to the general public. A family-based approach may contribute to aetiological research, and make pragmatic sense in clinical practice, but does not provide a scientific basis for a high-risk strategy of prevention.
One hundred hospitalized patients in Manila, Philippines with aseptic meningoencephalitis were screened for leptospirosis. On the basis of a microscopic agglutination titer of 1:1,600 or greater, the diagnosis was made in five cases, yet in no instance had leptospirosis been included in the differential diagnosis on admission to the hospital. Four of the five patients first noted neurologic symptoms during the second week of illness; two patients presented with encephalitis, two with meningitis and the fifth with hemiparesis. No case was complicated by renal dysfunction or jaundice. By the time of discharge from the hospital, two patients had recovered completely and the other three had markedly improved. Our data show that leptospirosis is an important but overlooked cause of aseptic meningoencephalitis in the Philippines. This is probably also the case in other parts of the tropics where Leptospira interrogans infection remains a significant public health problem.
The effect of a 7-day course of intravenous penicillin (6 million units/day) on severe, advanced leptospirosis was examined in a randomised, placebo-controlled, double-blind trial involving 42 patients. Every measurable aspect of the disease was favourably affected by penicillin. Fever lasted more than twice as long in the placebo group (11.6 [SD 8.34] days vs 4.7 [4.19] days, p less than 0.005), and by the fourth day after starting penicillin more than half the treatment group, but only 1 of 19 in the placebo group, were afebrile (p less than 0.005). Creatinine rises persisted more than thrice as long in the patients receiving only placebo (8.3 [8.46] days vs 2.7 [1.90] days; p less than 0.01). Penicillin also shortened the hospital stay and prevented leptospiruria. Intravenous penicillin should be given to patients with severe leptospirosis, even if therapy can be begun only late in the course of their disease.
Chloroquine (25 mg/kg over 3 d) was compared to quinine (10 mg/kg 3 times daily for 5 d) in 20 adult Filipino males with uncomplicated Plasmodium falciparum malaria in a double-blind, randomized trial. Asexual parasitaemia was cleared in all patients, with no statistically significant difference (P = 0.13) in the rate of clearance between the chloroquine-treated patients (76.1 +/- 29.3 h) and those receiving quinine (60.3 +/- 12.5 h). The duration of fever was also comparable (chloroquine 46.3 +/- 24.7 h; quinine 43.2 +/- 20.0 h; P = 0.76) and 40% of patients in each treatment group experienced mild side effects. Chloroquine, however, is cheaper and easier to administer. In vitro results were strikingly different. P. falciparum parasites from 4 quinine-treated patients were all sensitive to this compound in vitro, whereas 4 of the 5 isolates from the chloroquine group were resistant. Further comparisons of these two antimalarials are indicated, especially in cerebral malaria, and drug use policies should be based on clinical and parasitological response to treatment.
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Praziquantel undergoes extensive first-pass hepatic biotransformation, but there is little information on its disposition or toxicity when administered to patients with liver disease. To define the influence of liver disease on the pharmacokinetics of praziquantel, we administered it orally to 30 patients with proven Schistosoma japonicum infection whose liver disease was carefully assessed as being severe, moderate, or absent. Both the peak plasma concentration of praziquantel and the bioavailability (measured as the area under the plasma concentration time curve) were significantly greater in the two groups of patients with liver disease (P less than .005), as were the concentrations of the two identified metabolites of praziquantel. Mild side effects were associated with high peak concentrations of praziquantel, but a syndrome of severe abdominal pain followed by bloody diarrhea was not. Our results indicate that the side effects and bioavailability of praziquantel are increased in the presence of liver disease.
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Rapid diagnostic tests for tuberculous meningitis are urgently needed because delayed treatment increases the already high mortality rate of this disease. Direct acid-fast staining of cerebrospinal fluid is the only quick method generally available, but it lacks sensitivity. Therefore, we evaluated the use of an enzyme-linked immunosorbent assay (ELISA) to mycobacterial antigen and antibody in the cerebrospinal fluid of 29 patients with proven tuberculous meningitis, 83 patients with nontuberculous central nervous system infections, and 15 normal controls. The specificity of the test was 96%; the four false-positive results all occurred in patients with bacterial meningitis. Fifteen (52%) of 29 patients with tuberculous meningitis had either a positive antigen or antibody ELISA test, which was significantly more than the number of patients testing positive by direct staining (two of 29 positive; P less than .01). We therefore recommend using an ELISA to detect antigen and antibody but caution that because of limited sensitivity a negative test result does not exclude the diagnosis of tuberculous meningitis.
The effects of tourniquet application were prospectively studied in 36 hospitalized patients who developed neurotoxic symptoms after bites by the Philippine cobra (Naja naja philippinensis). Tourniquets had been applied in 94% of cases and delayed the onset of symptoms. Four patients were asymptomatic prior to the release of their tourniquet and in 11 patients symptoms worsened precipitously. Most importantly, 4 patients developed complete respiratory paralysis requiring artificial ventilation on its removal. Medical personnel seeing patients after a possible cobra bite should remove any tourniquet very gradually with both specific therapy and ventilatory support at hand. We recommend tourniquet application in the Philippines only after the bite of a definitely identified cobra and when removal can take place under controlled hospital conditions.
We studied 39 patients envenomed by the Philippine cobra (Naja naja philippinensis). Neurotoxicity occurred in 38 cases and was the predominant clinical feature. Respiratory paralysis developed in 19 patients, and was often rapid in onset--in 3 cases apnea occurred within 30 min of the bite. There were 2 deaths, both in patients who were moribund upon arrival at the hospital. Three patients developed necrosis, and 14 individuals with systemic symptoms had no local swelling. Both cardiotoxicity and reliable nonspecific signs of envenoming were absent. Bites by the Philippine cobra produce a distinctive clinical picture characterized by severe neurotoxicity of rapid onset and minimal local tissue damage.
Although human cases of leptospirosis have been reported from the Philippines, there is a lack of data on its prevalence. We therefore surveyed three rice-farming villages for the presence of leptospiral antibody. Out of 155 sera tested, 63 (43.6%) tested positive using the standard microagglutination test. Antibodies were more frequent in men than women (48 vs. 31%, respectively, p less than 0.01), and less common in the elderly. Exposure to leptospires occurs frequently in rice farmers, and leptospirosis is likely to be an underdiagnosed cause of both mild and severe febrile illness in the Philippines.
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244 outpatients and 100 hospitalized patients with confirmed Schistosoma japonicum infection were prospectively surveyed for the presence of nephropathy. There was no association between schistosomiasis and renal disease in the outpatient group. Three hospitalized patients had evidence of significant nephropathy, but this number was not significantly higher than in a control group of 100 hospitalized age and sex-matched control patients without schistosomiasis. One schistosomiasis patient with severe nephrotic syndrome underwent percutaneous renal biopsy. Neither S. japonicum antigen nor antibody was found in the biopsy specimen. 64 of the 100 hospitalized patients had portal hypertension; in 28 patients there was hepatic decompensation. Only one of these hepatosplenic patients had evidence of renal disease. Thus renal involvement was uncommon in patients presenting various manifestations of chronic S. japonicum infection, including those with severe hepatosplenic disease. These results contrast markedly with S. mansoni infection, in which nephropathy associated with advanced liver disease is a distinct, well-recognized clinical entity.
There is no information and therefore no consensus on how chloroquine should be administered to persons with severe malaria. Although widely considered dangerous, parenteral chloroquine is extensively used. We studied the acute disposition and toxicity of intravenous (iv), intramuscular (im), subcutaneous (sc), and oral chloroquine in 60 adult Zambian patients hospitalized with falciparum malaria. Plasma concentration profiles after parenteral administration were characterized by wide fluctuations between peak and trough values. Absorption of im and sc chloroquine was rapid, with a median time to peak concentration of 30 min and a peak plasma concentration five times higher than after oral administration. The pharmacokinetic data suggest that the acute toxicity of parenteral chloroquine is related to transiently high concentrations in blood and result from incomplete distribution out of a relatively small central compartment. Parenteral chloroquine may be administered safely by simply giving smaller, more-frequent doses than are currently used or, in the case of iv administration, by using continuous infusion.
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