Seven-day Course Research Articles

Teaching third-year medical students how to care for terminally ill patients.

Most medical schools in the United States introduce students to the care of dying patients. In most cases, there is no immediate practical application of the material, and many medical students find it very difficult to interact with a terminally ill person in a clinical situation. The authors describe a successful seven-day course offered annually since 1979 to third-year medical students. The course is an integrated program for teaching the students an effective way to deal with terminal illness, using lectures, audiovisual aids, and group and individual sessions to enhance self-awareness and a practical application of the material in a clinical setting.

10 Acute Myeloid Leukaemia: Recent Advances in Therapy

Over the past ten years, there have been substantial advances in the treatment of AML. Intensive induction chemotherapy using seven-day courses of cytarabine and daunorubicin or amsacrine produce remission in 60-85% of patients. Median remission duration is 9-16 months. In some series, 20-40% of patients are in continuous remission for two years or more; many of these patients remain in remission for five years or longer and some may be cured. Bone marrow transplantation has evolved as a useful therapeutic modality capable of achieving long-term survival in some circumstances in which chemotherapy is relatively ineffective. Its precise role in the initial therapy of AML remains to be defined but it is likely to be beneficial in selected patients. These data indicate substantial recent progress in the treatment of this disease which was almost uniformly fatal 30 years ago. The fact that most patients relapse within 1-2 years reflects a lack of progress in developing effective postremission therapy. Maintenance chemotherapy, immunotherapy and CNS prophylaxis have little role in AML. It is unclear whether consolidation or intensification extend remissions or increase the proportion of long-term survivors; controlled randomized trials should answer this question within the next few years. Future progress in the treatment of AML awaits the development of more sensitive methods for detecting residual leukaemia, more effective use of current therapeutic modalities and the introduction of new effective drugs. Most data suggest that early intensive treatment is of key importance for achieving cures. We cannot presently distinguish, however, between patients cured by initial treatment and those who require further chemotherapy.

Abatement of sézary syndrome lesions following treatment with acyclovir

Sézary syndrome is a malignant form of cutaneous T cell lymphoma in which patients characteristically present with generalized pruritic erythroderma and large numbers of circulating Sézary cells in the peripheral blood. Several previous studies have proposed that viruses may play a role in the cause of cutaneous T cell lymphoma. This report describes a 68-year-old man with Sézary syndrome who received a seven-day course of intravenous acyclovir for treatment of disseminated herpes zoster and was noted to have almost complete disappearance of generalized erythroderma and pruritus. Since acyclovir has been shown to selectively inhibit viral DNA polymerase, the observed clinical response is strong evidence that viruses play a role in the cause of cutaneous T cell lymphoma. Mechanisms that could explain the observed response are discussed, and further studies on the utility of antiviral agents for treatment of cutaneous T cell lymphoma and on possible inhibitory effects of acyclovir on retroviruses are recommended.

Bacterial Vaginosis-Reply

In Reply.— In response to comments by Drs Mengel and Pennachio, our study has a clinical focus—comparing two medication regimens (a single 2-g vs seven-day course of metronidazole) in the treatment of women who presented with symptoms associated with bacterial vaginosis. The patients were predominantly young white women receiving medical care at a community-based family practice residency clinic. The randomly assigned treatment groups were similar in terms of race, age, and parity. Risk factors for bacterial vaginosis were not evaluated. Selection based on risk factors would have invalidated the randomization and added additional assumptions to the interpretation of results. Furthermore, risk factors only provide various degrees of predictability for the occurrence of disease in a population—all the subjects in our study had the disease and were symptomatic. The study by Amsel et al 1 identified only two risk factors (use of intrauterine devices and history of previous Trichomonas vaginalis infection) that

Comparison of Single-Dose vs One-Week Course of Metronidazole for Symptomatic Bacterial Vaginosis

In a prospective, single-blind, randomized study, a single 2-g dose of metronidazole was compared with a seven-day course of 500 mg given twice daily in the treatment of symptomatic vaginal discharge associated with Gardnerella vaginalis. Based on resolution of symptoms and on cultures negative for G vaginalis, 86% (40/46) of women treated with the single dose and 97% (35/36) of women treated with the seven-day course were considered cured at seven to ten days after treatment. Evaluation at 21 days after treatment, however, indicated that only 46% (16/34) of patients treated with the single 2-g dose were considered cured compared with 86% (26/30) of those treated with the seven-day course. Treatment of sexual contacts did not significantly improve cure rates in either group.

Investigation into the immunologic cross-reactivity of aztreonam with other beta-lactam antibiotics

The cross-reactivity between the monobactam antibiotic aztreonam and the commonly used beta-lactam antibiotics, penicillins, and cephalosporins was investigated. Antibodies to aztreonam, penicillin, and cephalothin were raised in rabbits. The ability of the homologous or heterologous drug or drug conjugates to inhibit antibody binding was assessed in a solid-phase radioimmunoassay. Aztreonam demonstrated very little ability to interact with anti-penicillin or anti-cephalothin antibodies as it required 10,000-fold higher concentrations than other beta-lactams to achieve equivalent blocking. Similarly, penicillin and cephalothin conjugates did not cross-react, to any significant degree, with anti-aztreonam rabbit antiserums. Interestingly, free aztreonam was as effective as conjugated aztreonam in reacting with antibodies raised against conjugated aztreonam. This result suggested that, in contrast to the other beta-lactams, antibodies to aztreonam recognize the side chain rather than the nuclear structures. Studies with other beta-lactam analogs confirmed that the IgG rabbit anti-aztreonam binding was indeed side chain-specific. Thirty-six volunteers were given a seven-day course of therapeutic doses of aztreonam and in none did any detectable IgE anti-aztreonam antibodies develop. Four of these subjects had evidence of preexisting IgG antibodies cross-reactive with aztreonam, but the levels rose in only one patient following drug exposure. This human IgG anti-aztreonam was also directed to the side chain and did not cross-react with cephalothin or penicillin. The ability of aztreonam to cross-react with human IgE to various penicillin determinants was also investigated. Aztreonam determinants analogous to the penicillin determinants (penicillin, penicilloyl, and penicilloate) were constructed and the maximal concentration that did not evoke false-positive skin test results was determined to be 6 × 10 −3mol/liter. None of 41 patients with documented IgE-reactive skin tests to various penicillin determinants concurrently demonstrated reproducible reactivity to any aztreonam reagents. IgE antipenicilloyl antibodies from three persons were also tested in vitro for their ability to cross-react with conjugated or free aztreonam. Minimal, if any, reactivity was observed between the IgE anti-penicilloyl and any of the aztreonam materials. These results indicate that there is very little cross-reactivity between the monobactam aztreonam and other beta-lactam antibiotics.

Urinary tract infection among women attending a clinic for sexually transmitted diseases.

The symptoms, signs, and laboratory findings for 69 women who were seen at a sexually transmitted disease (STD) clinic and who had acute urinary tract infection (UTI) were compared with those for women who had vaginitis, gonorrhea, or chlamydial infection. Escherichia coli and Staphylococcus saprophyticus were the two most common causes of acute cystitis in this population and accounted for 62 (90%) of 69 infections. Forty-three percent of the women had positive tests for antibody-coated bacteria (ACB), an observation implying renal infection although symptoms of upper tract infection were infrequent. Frequency, urgency, dysuria, and suprapubic tenderness were significantly associated with cystitis, whereas vaginal discharge and vulvar itching were associated with vaginitis. There was, however, considerable overlap in symptoms among the four groups of women, and their accurate differentiation required objective information based upon pelvic examination, examination of vaginal fluid, and urinalysis. In the absence of vaginitis on wet mount and mucopurulent cervicitis on examination, pyuria, as determined by examination of centrifuged urine, had an 88% sensitivity, 76% specificity, 61% positive predictive value, and 93% negative predictive value for acute UTI. Because of the high prevalence of positive ACB tests and the possibility that infection with Chlamydia trachomatis and/or Neisseria gonorrhoeae may be mistaken for cystitis, we prefer a five- to seven-day course of antibiotics over single-dose therapy for treatment of patients with possible UTI in the setting of an STD clinic.

Use of Liver Function Tests as Predictors of Rifampicin Metabolism in Cirrhosis

Normal subjects taking rifampicin regularly, show a fall in serum and urinary drug concentrations from enzyme induction and increased biliary excretion. In cirrhosis, hepatocellular dysfunction and impaired biliary excretion may prevent these changes, but there is little information on how the drug should be prescribed in such patients. Serum and urinary rifampicin concentrations were therefore measured in thirteen patients and five controls during a seven-day course (600 mg/day). In controls, peak serum concentrations on Day 7 were lower than on Day 1 (7.0 +/- 3.0 and 8.0 +/- 1.0 microgram/ml respectively) and this was also the case for nine cirrhotic patients with mild impairment of liver function (6.0 +/- 1.0 and 11.0 +/- 2.0 microgram/ml (p less than 0.02). In both groups there was an accompanying fall in urinary rifampicin excretion due to a decrease in desacetylrifampicin excretion. In the remaining four cirrhotic patients, peak serum rifampicin levels rose from 11.0 +/- 5.0 to 17.0 +/- 6.0 microgram/ml and urinary excretion of desacetylrifampicin did not fall. Although values for serum albumin and prothrombin time were of limited value in predicting drug accumulation, pretreatment levels of bilirubin exceeding 50 mumol/l were present in all four patients showing an increase in serum rifampicin concentration. Furthermore, only in this group was there a rise in serum bilirubin during treatment, almost certainly the result of competition between rifampicin and bilirubin for hepatic uptake and excretion. In all patients with cirrhosis, bilirubin concentrations exceeding 50 mumol/l should be an indication for reduction of rifampicin dosage.

Persistent Infection of a Posttraumatic Phycomycotic Infection

To the Editor. —In May 1978, Schwartz et al 1 documented the ocular effects of a posttraumatic phycomycotic infection on the anterior segment of the left eye of a 26-year-old man. We now wish to report follow-up clinical data and histologic evidence of localized persistence of the infection in the anterior segment and donor cornea two years later. The patient initially manifested a Rhizopus (phycomycosis) infection of the anterior segment of his left eye two months following a perforating injury with a soil-contaminated screwdriver. After intensive but unsuccessful antifungal medical therapy, a combined 10-mm penetrating keratoplasty and planned extracapsular cataract extraction was performed (Jan 7, 1977), which included the removal of an organized anterior chamber cast and portions of necrotic iris. Postoperatively, the patient received a seven-day course of intravenous amphotericin B and topical natamycin drops, and was discharged from the hospital on Jan 25, 1977, with a clinically quiet

Effect of theophylline on allergen skin tests

The effect of theophylline on allergen-induced wheal and flare responses of 15 adults with atopy was studied in a double-blind, crossover study. After intradermal skin tests to determine baseline wheal and flare responses, subjects were assigned randomly to consecutive seven-day courses of theophylline 16 mg/kg/day (as Aminophylline USP) then of placebo, or the reverse. Subjects were tested with mixed weeds and mixed grasses allergens and with histamine diphosphate, codeine phosphate and a buffered saline control. Skin tests were repeated two hours after the last dose of theophylline or placebo in each treatment course, and serum theophylline concentrations were measured. The surface areas of the wheal and flare responses were measured by planimetry. No statistically significant difference (p greater than 0.05) was found between theophylline and placebo in the suppression of the allergen-induced wheal and flare response. Serum concentrations of theophylline were within the accepted therapeutic range. In therapeutic steady-state serum concentrations, theophylline does not significantly suppress allergen-induced wheal and flare response of atopic patients, and withdrawal of the drug before skin testing is unnecessary.

Energy flow in a woodland ecosystem

The study of energy flow in a woodland ecosystem was attempted during a seven-day field course, using simple equipment. It is possible to quantify or estimate many of the components, and the methods used are described. Suggestions are made for maximizing educational return from the available time and labour.

Seven-Day Clotrimazole Therapy for Vulvovaginal Candidiasis

There were 150 patients with mycologically proven vulvovaginal candidiasis in a randomized, non-cross-over study which compared seven-and 14-day treatment courses of clotrimazole vaginal tablets (Gyne-Lotrimin) with a 14-day treatment course of miconazole nitrate 2% vaginal cream (Monistat). Adequate data for analyses were obtained for 117 patients. When patients were reexamined four or more weeks after completion of therapy, success rates, based on clinical and mycologic criteria, were: 88% for patients treated with clotrimazole for seven days, 84% for clotrimazole 14-day treatment, and 78% for miconazole nitrate 14-day treatment. There were no drug-related adverse reactions. Thus a seven-day course of therapy with clotrimazole is effective as is a 14-day course of either clotrimazole or miconazole nitrate 2% for the treatment of Candida vaginitis. Statistical analysis revealed no significant differences among the clotrimazole seven-and 14-day treatment groups and the miconazole nitrate 14-day treatment group. The shorter period of administration required for this new antifungal agent should result in better patient compliance and an improved success rate in the rate in the treatment of this frequently encountered infection.

Hemostasis, Antipyretics, and Mild Analgesics

The effects of acetaminophen and aspirin on the hemostatic process were compared. First, a single 975-mg or 1,950-mg dose of acetaminophen had no effect on bleeding time, platelet aggregation, or platelet factor 3 release in normal volunteers, in contrast with the significant increase in bleeding time and abnormalities in platelet aggregation caused by aspirin. Second, a seven-day course of either aspirin or acetaminophen, 1,950 mg daily, had no effect on specific coagulation factors, platelet factor 3 availability, or the fibrinolytic mechanism. Finally, a six-week course of acetaminophen, 1,950 mg daily, had no effect on the bleeding time in three hemophiliac patients and no effect on bleeding time, platelet aggregation, or platelet adhesion in four normal subjects. Acetaminophen is an antipyretic and mild analgesic that may be useful when influence on hemostasis is undesirable. (JAMA235:613-616, 1976)

Volunteer and clinical studies with carfecillin: a new orally administered ester of carbenicillin.

Blood and urine levels of carbenicillin were measured in 10 healthy volunteers and four patients with renal failure after single and multiple oral dose of carfecillin. Urinary levels after 1000-mg doses in healthy subjects were considered sufficient for treatment of Pseudomonas aeruginosa urinary infections, but the serum levels were too low for chemotherapy of systemic infections with this organism even in severe renal failure. Urinary infections were treated in 35 inpatients with a seven-day course of carfecillin. The infection was eradicated in 21 cases (60%). In 12 cases the pathogen was Ps. aeruginosa, which was eradicated from eight patients (67%). Many patients had severe urinary tract disease. Side effects were virtually absent.

KINKY HAIR SYNDROME: RESPONSE TO COPPER THERAPY

A 3-month-old male with kinky hair syndrome was given copper salts and purified ceruloplasmin, and the clinical and chemical responses measured. Initial plasma copper concentration was l5µ/100 ml and ceruloplasmin was undetectable. A seven-day course of oral cupric sulfate did not raise plasma copper or ceruloplasmin concentrations. After intravenous administration of cupric acetate on two occasions ceruloplasmin was detectable by chemical and immunological assays. Intravenous administration of purified human ceruloplasmin raised plasma ceruloplasmin levels acutely to normal. The in vivo half-life of this ceruloplasmin was within the range observed in infants with nutritional copper deficiency. These results support the contention of Danks et al. (Lancet, 1:1100, 1972) that intestinal copper absorption is defective in this syndrome. They further demonstrate that ceruloplasmin synthesis and decay appear normal when copper is available. The patient's clinical condition showed no change after copper and ceruloplasmin administration, suggesting that the neurological damage was irreversible. The possibility remains that earlier administration of copper or ceruloplasmin might be effective.

Strongyloides stercoralis autoinfection.

To the Editor.— A case of asymptomatic Strongyloides stercoralis autoinfection with marked eosinophilia appeared in a patient absent from endemic areas for 23 years. Report of a Case.— A 37-year-old Puerto Rican man had departed from Puerto Rico at age 14 years, and has lived continuously in New York city since. On admission, he admitted to heavy alcohol consumption and complained of vomiting, weakness, icterus, and increasing abdominal girth. Abnormal physical findings included a liver palpable 7 cm below the right costal margin, and pedal edema (2+) bilaterally. The white blood cell count (WBC) was 8,200/cu mm, with 84% neutrophils, 14% lymphocytes, 2% monocytes, and no eosinophils. The patient was treated with fluids intravenously and all laboratory data returned to normal. A liver biopsy revealed cirrhosis and alcoholic hepatitis. The patient became asymptomatic and afebrile and was given a seven-day course of ampicillin (250 mg by mouth every six hours)

Enhancement by phenobarbital and diphenylhydantoin of carbon monoxide production in normal man.

Abstract Nine normal human subjects were given a seven-day course of phenobarbital or diphenylhydantoin. With phenobarbital and diphenylhydantoin respectively, total body heme, as estimated by carbon monoxide dilution, rose to an average of 114.8 (p less than 0.05) and 109 (p less than 0.05) per cent of control levels. Rates of heme catabolism, determined by measurement of rates of carbon monoxide production, increased an average of 174 and 214 per cent of normal (p less than 0.01) with these two agents. The agents appear to have induced hepatic heme, and after induction, catabolism of hepatic heme contributed over 50 per cent of the total carbon monoxide production.

The Effects of Lithium Salts on Brain Activity in the Cat

Two sets of experiments were conducted to study the effects of lithium on the gross electrical activity of the cat brain. The first series, designed to study acute effects by means of recording evoked potentials using encephale isolé cats, suggests that the orbito-frontal cortex is a primary brain locus for the immediate effects of lithium. The second series of experiments, designed to study chronic effects, suggests that lithium produces widespread EEG slowing after it has been administered for seven days; marked behavioral changes were also observed in these cats following the seven-day course of lithium administration.

LONG-TERM FOLLOW-UP OF BACTERIURIA IN PREGNANCY

285 women found to have bacteriuria during pregnancy were treated and subsequently seen at frequent intervals until discharge from the postnatal clinic, when all had sterile urine. Of these patients 157 were re-examined two to four years later and 43 (27%) had bacteriuria. These 43 patients could be further divided into two groups according to whether or not they had responded to the first course of chemotherapy given during pregnancy, and this showed that infection was more than twice as likely to be present in the group who had failed than those who had responded. Increased urinary white-blood-cell excretion was found in 31 (72%) of the 43 women but only 21 (49%) complained of urinary symptoms. Radiological abnormalities were found at long-term follow-up in 26 (37%) of the 71 women examined, and these were also related to failure of treatment early in pregnancy. Chronic pyelonephritis was detected in 11 women and in 10 of these the original antenatal infection had proved resistant to treatment. Patients infected at long-term follow-up were given a seven-day course of treatment and 56% responded. However, further analysis showed that those women who had previously failed the first course of treatment in pregnancy were also much less likely to respond. The characteristics of the organisms isolated from 56% of the patients with infection at follow-up suggested that a single episode of infection had not persisted but rather that these patients were susceptible to recurrent episodes of infection. In the other 44% of patients the organism was indistinguishable from that isolated in pregnancy.

Treatment of enterobiasis and ascariasis with piperazine.

• Pinworm infestation in 60 patients was treated with piperazine citrate by mouth in a seven-day course. No advantages were seen in prolonging the treatment to 10 or 14 days, in dividing the daily dose, or in substituting piperazine phosphate or calcium dipiperazine dicitrate. Ascariasis in 46 patients was treated with a single dose of piperazine citrate, and 34 were cured by this one-day treatment. A two-day treatment cured 50 out of 53 patients. The timing of the dose, whether before or after breakfast, had no discernible influence on the result. Side-reactions in the form of urticaria, nausea, or diarrhea were seen but rarely in 400 patients who received the recommended dosage of 50 to 75 mg. of piperazine (calculated as the hexahydrate) per kilogram of body weight per day.