Airway closure during mixed apneas in preterm infants: is respiratory effort necessary?

We report the ability of azithromycin in combination with quinine to eliminate the Babesia infection in a native Taiwanese woman. Failure of elimination of the babesial infection was observed two weeks after treating with standard regimen of oral quinine plus intravenous clindamycin for a 10-day course of therapy. Azithromycin in place of clindamycin was administered for another 10-day course of therapy two months following initial treatment. Clearance of Babesia parasites was observed and verified by hamster inoculation. These results suggest that azithromycin plus quinine should be considered as an alternative therapy for human babesiosis, especially in the failure of treatment with standard regimens.     

Curing of chloroquine-resistant malaria with clindamycin

A randomized comparative trial for treating adult patients with Plasmodium falciparum malaria was performed in Lambarene, Gabon. Forty-two patients received chloroquine (25 mg/kg for 48 hr) and 38 patients received clindamycin (5 mg/kg twice a day, for five days). Chloroquine treatment cured 15 patients (36%). Twenty patients (48%) showed recrudescent malaria by day 28 of follow-up (RI resistance) and seven patients (17%) showed persistent parasitemia after chloroquine treatment (RII/III resistance). In contrast, clindamycin treatment cured 37 of 38 patients (97%) and only one (3%) showed a recrudescence by day 28 (P < 0.001). Although the parasite clearance time was significantly longer after clindamycin treatment (median five days, range 3-6) than after chloroquine treatment (median four days, range 2-8) (P < 0.01), no differences were seen in the duration of symptoms after chemotherapy. In both treatment groups, no severe side effects occurred. Clindamycin can be used as a safe alternative to achieve radical cure in semi-immune adult patients with chloroquine-resistant P. falciparum malaria in Central Africa.     

The effect of commencing combination antiretroviral therapy soon after human immunodeficiency virus type 1 infection on viral replication and antiviral immune responses

Twelve subjects were treated with zidovudine, lamivudine, and ritonavir within 90 days of onset of symptoms of acute infection to determine whether human immunodeficiency virus type 1 (HIV-1) infection could be eradicated from an infected host. In adherent subjects, with or without modifications due to intolerance, viral replication was suppressed during the 24-month treatment period. Durable suppression reduced levels of HIV-1-specific antibodies and cytotoxic T lymphocyte responses in selected subjects. Proviral DNA in mononuclear cells uniformly persisted. The persistence of HIV-1 RNA expression in lymphoid tissues and peripheral blood mononuclear cells suggests that elimination of this residual pool of virus should be achieved before considering adjustments in antiretroviral therapeutic regimens. In addition, given the reduction in levels of virus-specific immune responses, it would seem prudent to consider enhancing these responses using vaccine strategies prior to the withdrawal of antiviral therapy.     

The pharmacokinetics of quinine in patients with hepatitis

The pharmacokinetics of quinine were studied in six patients with hepatitis B infection (during acute and convalescent periods) and six healthy subjects. A single 10 mg kg-1 dose of quinine was given intravenously over 2 h. Pharmacokinetic parameters of quinine during the acute phase of the infection were not different from those during the recovery phase. However, when compared with those obtained from healthy subjects, significant changes were found. The terminal elimination half-life was prolonged (17 and 15 vs 10 h) and clearance was lower (2.9 and 2.3 vs 3.5 ml min-1 kg-1). Unbound quinine concentration in plasma at 2 h was approximately 10% of the total concentration in all subjects in the three study groups. A prolonged QTc interval (< 25%) was observed in all groups. The present data suggest that current dosage regimens of quinine used in the treatment of falciparum malaria may not be suitable for malaria patients with acute hepatitis or those who have had hepatitis within the past 3 months.     

Immunoglobulin therapy in Gilles de la Tourette syndrome

It has known for a long time that Sydenham's chorea and tics, as seen in Gilles de la Tourette's syndrome (GTS), are phenomenologically very similar. Tics may occur as symptoms of acute Sydenham's chorea or persist over years as residual symptoms. Investigating of children suffering from GTS, including obsessive-compulsive symptoms, have provided signs of a poststreptococcal autoimmune process but also shown that treatment based on immunological interventions has been effective. We treated a 14-year-old boy showing all diagnostic criteria of GTS, familial susceptibility, and an increase in the antibody titer of streptococcal antigens with 75 immunoglobulins i.v. over 5 days. Response to this therapy was good regarding motor tics, vocal tics, and behavioral symptoms such as disturbed impulse control which still persisted after 9 months. These findings and the successful therapy underline reports of the literature and point to a pathogenetic mechanism of an immunologically triggered disturbance of the striatal dopaminergic system, at least in a subgroup of GTS.     

Pilomatricoma in elderly individuals

We report the clinical course of five adult patients with chronic Chagas' disease (Cd) who underwent BMT. Two patients with non-Hodgkin's lymphoma and one with ALL received an ABMT. Allogeneic BMT was performed in two patients with AML and CML respectively. One donor had chronic Cd. Samples of peripheral blood for parasite investigation by the Strout method, blood culture, and immunological studies by indirect immunofluorescent assay, ELISA and indirect hemagglutination tests were performed weekly from the start of chemotherapy until day +60 for ABMT and during the period of immunosuppression for allogeneic BMT. No prophylaxis was given to any of these patients. In only one ABMT patient were trypomastigotes detected early by blood culture without symptoms of reactivation. Benznidazole as preemptive treatment was administered at 5-8 mg/kg/daily for 30 days. Parasitemia was rapidly cleared and at the end of therapy xenodiagnosis was negative. The other Cd patients showed no evidence of relapse of parasitemia or signs and symptoms of reactivation. In brief, evidence of Cd should be sought in all BMT patients coming from endemic areas because parasitemia and reactivation are potential complications during the period of neutropenia and immunosuppression. The strategy used for early detection and treatment of parasitemia and reactivation was safe and effective.     

Atovaquone and proguanil for the treatment of malaria in Brazil

The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil with the standard regimen of quinine plus tetracycline for the treatment of uncomplicated falciparum malaria. The study was designed as an open, randomized study of men presenting with symptoms of uncomplicated malaria and thick-smear slide confirmation of parasitemia (1000-100,000 ring forms/microL). Subjects were hospitalized for 28 days to insure medication compliance and to rule out the possibility of reinfections. With 77 patients in each group, the cure rates were 98.7% and 100% for atovaquone plus proguanil and quinine plus tetracycline, respectively. The parasite clearance times (mean, 56 h) and fever clearance times (mean, 19 h) were significantly shorter in the atovaquone plus proguanil group, and there were significantly fewer side effects in the atovaquone plus proguanil group. Atovaquone plus proguanil is an efficacious, easily administered, safe regimen for the treatment of uncomplicated, multidrug-resistant falciparum malaria in Brazil.     

Clindamycin in persisting streptococcal pharyngotonsillitis after penicillin treatment

239 patients with streptococcal pharyngotonsillitis completed treatment with phenoxymethyl penicillin 12.5 mg per kg body weight b.i.d. for 10 days. At examination after completing therapy, throat specimens from 53 patients (22%) yielded growth of group A streptococci of the same. T-type as the initial culture (bacterial treatment failure). 20 of these 53 (38%) had symptoms and signs of tonsillitis (clinical and bacterial treatment failure). 48 of the patients with bacterial failure were randomly allocated to phenoxymethyl penicillin or clindamycin in an open design; 22 of them received a second course of phenoxymethyl penicillin for 10 days and 26 were given clindamycin, 6.5 mg per kg body weight b.i.d. (children) or 300 mg t.i.d. (adults) for 10 days. After completing their treatment, 14 of 22 patients (64%) given phenoxymethyl penicillin harboured the same T-type as in the previous two cultures, while group A streptococci were not recovered from any of the 26 patients receiving clindamycin. In patients with clinical failure after phenoxymethyl penicillin treatment, a new course with this drug is not motivated. In that situation clindamycin seems to be an efficient choice.     

Quantitative polymerase chain reaction to predict occurrence of symptomatic cytomegalovirus infection and assess response to ganciclovir therapy in renal transplant recipients

Cytomegalovirus (CMV) DNA levels were measured by quantitative-competitive polymerase chain reaction (PCR) in weekly leukocyte samples from 50 renal transplant recipients, including 23 with symptomatic and 27 with asymptomatic CMV infection. Peak and week 4 CMV DNA levels were higher in symptomatic subjects (P = .07 and .02, respectively). In a logistic regression model, the logarithm of the week 4 level independently predicted symptomatic infection (odds ratio, 1.78 for a 1 log10 increase; 95% confidence interval, 1.14-2.78; P = .01). All subjects whose week 4 level exceeded 1000 copies/100,000 leukocytes developed symptoms. In subjects with adequate samples for analysis, CMV levels declined exponentially with ganciclovir treatment, with an average half-life of 3.3 days. Levels exceeding 10,000 copies were associated with prolonged time to clearing of CMV DNA. Potential clinical applications of quantitative CMV PCR include predicting occurrence of symptomatic first episodes after transplantation and individualizing duration of antiviral therapy.     

Effect of foscarnet on quantities of cytomegalovirus and human immunodeficiency virus in blood of persons with AIDS

Four intravenous dosages of foscarnet given for 10 days were compared with no therapy in persons with AIDS who had asymptomatic cytomegalovirus (CMV) viremia. CMV viremia was quantitated by endpoint cell dilution microcultures, pp65 antigenemia assay, and measurement of CMV DNA in peripheral blood leukocytes by a quantitative-competitive PCR. Human immunodeficiency virus type 1 (HIV-1) viremia was quantitated by endpoint cell dilution microculture, serum p24 antigen assay, and PCR for HIV-1 RNA in plasma. Twenty-seven subjects who had received a median of 22 months of nucleoside antiretroviral therapy were enrolled. Twenty-two subjects received foscarnet, which was well tolerated and decreased the CMV burden, as reflected by all three indicator assays. During the 10 days of dosing, the level of CMV viremia, as measured by 50 percent tissue culture infective doses, decreased from 117.5 to 12.7 (P = 0.001), the amount of CMV DNA decreased from 20,328 copies to 622 copies per 150,000 leukocytes (P = 0.02), and the level of CMV pp65 antigenemia decreased from 14.9 to 1.6 positive peripheral blood mononuclear cells per 50,000 leukocytes (P = 0.008). A significant pharmacodynamic relationship was found between the peak foscarnet concentration and a decrease in the level of CMV antigenemia (P < 0.05). Foscarnet had no effect on quantitative HIV-1 microcultures during the 10 days of treatment, but the HIV-1 p24 antigen level in serum decreased significantly, from 454 to 305 pg/ml (P = 0.01). Also, a significant pharmacodynamic relationship was seen between plasma HIV-1 RNA concentrations and both peak foscarnet concentration (P < 0.01) and the area under the foscarnet time-concentration curve (P < 0.05). Reductions in the levels of CMV and HIV-1 viremia correlated quantitatively with systemic exposure to foscarnet, whereas control subjects actually experienced an increase in CMV and HIV-1 burdens. The dual antiviral activity of foscarnet shown in this trial encourages investigation of its use in combination with other antiretroviral therapies for persons with AIDS.     

Health status and health care costs for publicly funded patients with schizophrenia started on clozapine

OBJECTIVE: The study examined the effect of clozapine treatment on the health care costs and health status of people with schizophrenia who are supported by public funds. METHODS: Thirty-three patients with schizophrenia hospitalized in a state facility were interviewed within one week of starting clozapine and six months later. Health status was assessed with four clinical rating scales measuring severity of psychopathology, negative symptoms, depression, and quality of life. Cost and health care utilization data were collected for the six months before and after initiation of clozapine. RESULTS: Only 52 percent of the subjects stayed on clozapine for six months. Subjects who continued on clozapine were more likely to be discharged within six months than those who did not continue. Six months after clozapine was started, health care costs showed a sayings of $11,464 per person, even after adjustment for pretreatment costs, and health status was improved. CONCLUSIONS: For subjects who continued on clozapine for six months, clozapine treatment was associated with reduced days of psychiatric hospital care, reduced overall costs despite increased outpatient treatment and residential costs, and improved health status.     

Transdermal absorption of clindamycin and tretinoin from topically applied anti-acne formulations in man

The percutaneous absorption of clindamycin was studied in healthy male volunteers, comparing two investigative clindamycin (% w/v)/tretinoin (0.025% w/v) gels, containing clindamycin phosphate ester and clindamycin HCl, respectively, relative to a clindamycin phosphate lotion (1% clindamycin; Dalacin T). Formulations were applied daily for 5 days on the face, according to a balanced complete block design. Redness of the skin was scored visually, and blood and urine were collected. Clindamycin plasma levels did not exceed the limit of quantification (5 ng mL(-1)) with the clindamycin phosphate formulations, but one volunteer who received the clindamycin HCl/tretinoin gel showed plasma levels of up to 13 ng mL(-1). Clindamycin urinary excretion for 12 h after application of the clindamycin phosphate/tretinoin gel was comparable to the values of the reference lotion, whereas the clindamycin HCl/tretinoin gel gave significantly higher values. Erythema appeared to be associated with increased urinary excretion. The formulations were tolerated well. In a separate clinical pilot study in acne patients, the transdermal uptake of tretinoin and clindamycin from the clindamycin phosphate/tretinoin gel was monitored. Plasma samples were collected after 4 and 12 weeks of daily treatment. None of the study plasma samples contained measurable tretinoin levels. Clindamycin levels were not quantifiable in the majority (87%) of samples, the highest plasma level was 11 ng mL(-1). The chemical form of clindamycin proved to modulate skin irritation and percutaneous uptake of clindamycin from a gel formulation in healthy subjects. There was no indications for a notable transdermal uptake of tretinoin during daily application of the gel in patients, nor for an enhancing effect of tretinoin on clindamycin uptake.     

Suspected lamotrigine-induced toxic epidermal necrolysis

OBJECTIVE: To describe a patient who developed toxic epidermal necrolysis (TEN) possibly secondary to lamotrigine use. CASE SUMMARY: A 74-year-old white man with a history of probable complex partial seizures was admitted to the neurology service for a prolonged postictal state. His antiepileptic regimen was changed while he was in the hospital to include lamotrigine. After 19 days of hospitalization and 14 days of lamotrigine therapy, the patient became febrile. The next day he developed a rash which progressed within 4 days to TEN, diagnosed by skin biopsy. All suspected drugs were discontinued, including lamotrigine. The patient was treated with hydrotherapy in the burn unit. His symptoms improved and he was discharged from the hospital 26 days after the rash developed. DISCUSSION: During lamotrigine's premarketing clinical trials, the manufacturer reported several cases of Stevens-Johnson syndrome and TEN. There are several published case reports of lamotrigine-induced severe skin reactions. All of these reports included patients being treated with both valproic acid and lamotrigine. Our patient was exposed to phenytoin, carbamazepine, clindamycin, and lamotrigine, but not valproic acid. The patient reported prior use of phenytoin with no skin rash. Carbamazepine was the antiepileptic drug the patient was maintained on prior to his hospital admission, and the symptoms of TEN resolved while he was still receiving carbamazepine. The patient received only two doses of clindamycin, which makes this agent an unlikely cause of TEN. CONCLUSIONS: Because of the temporal relationship of the onset of the patient's rash and several drugs that are known to cause severe rashes, it is not certain which drug was the definite culprit. However, based on the evidence from the literature, lamotrigine appears to be the causative agent.     

Recurrent colitis following antibiotic-associated pseudomembranous colitis

A patient who developed severe pseudomembranous colitis following clindamycin therapy, and who went on to have recurrent attacks of non-specific colitis, histologically confirmed over the following 19 months, is described.     

Identification of a subpopulation of immune Nigerian adult volunteers by antibodies to the circumsporozoite protein of Plasmodium falciparum

Collections of human sera from malaria-endemic areas would be valuable for identifying and characterizing antigens as malaria vaccine candidates if the contributing serum donors' ability to resist infection were fully characterized. We prepared such a serum collection from 26 apparently immune Nigerian adults who failed to develop patent parasitemia for at least 20 weeks following a documented increase in antibodies to the circumsporozoite protein (CSP) from Plasmodium falciparum. Volunteers were evaluated five times per week for malaria symptoms and bimonthly for parasites by examining thick blood smears. The incidence rate over 13 months for the cohort was 42% (47 malaria-confirmed volunteers) and the risk of infection was 1.3 infections/year. Responses to CSP did not correlate with protection. Because antibody responses to antigens other than CSP may be associated with protection, the sera from these immune individuals may be useful for identifying and characterizing other potential malaria vaccine candidates.     

Is routine post-operative surveillance for cytomegalovirus infection following heart transplantation necessary?

OBJECTIVE: Cytomegalovirus infection (CMV) is an important cause of morbidity and mortality following cardiac transplantation. The purpose of the present study was to ascertain whether routine post-operative screening for CMV infection influenced clinical management. METHODS: Laboratory and case notes of 220 patients who received cardiac transplantation between November 1986 and October 1996 were reviewed. The range of follow-up was one to 120 (median 36) months. CMV surveillance involved blood tests for early antigen detection weekly for the first 6 post-operative weeks, fortnightly thereafter until the end of the third post-operative month and every 6 weeks to the end of the first post-operative year. Otherwise monitoring was performed if the patients had clinical symptoms suggestive of CMV infection. CMV sero-negative IgG recipients (R) of sero-positive IgG donor (D) organs and/or blood products received hyper-immune gammaglobulin for the first three post-operative months. Four patient groups were noted, namely R+D+ (59 patients), R+D- (70 patients), R-D+ (35 patients) and R-D- (56 patients). RESULTS: CMV antigenaemia was present in 40% (89) of patients and 48% (43) of these patients developed clinical features of CMV infection and received ganciclovir therapy. The distribution of clinical CMV infection requiring treatment was 25% (9/35) in the R+D- group, 50% (16/32) in the R+D+ group and 85% (18/22) in the R-D+ group. None of the patients in the R-D- group developed CMV antigenaemia. Forty six (52%) patients who were CMV antigen positive but who did not develop symptoms were not treated with ganciclovir and have remained well. CONCLUSION: Our results suggest that routine screening for CMV following cardiac transplantation is unnecessary. Surveillance did not result in the instigation of treatment for CMV unless there were associated clinical features of CMV infection.     

Course of panic disorder during pregnancy and the puerperium: a preliminary study

Pregnancy has been referred to as a time of well-being for patients with psychiatric disorder. However, this impression is derived primarily from anecdotal reports and retrospective studies, rather than systematic prospective evaluation. In this study, 10 pregnant women with previous histories of panic disorder were evaluated prospectively across pregnancy and the postpartum period using the Structured Clinical Interview for DSM-III-R and the Clinical Global Impression. Information regarding pharmacotherapy received was also recorded. Seven of 10 subjects continued to meet DSM-III-R criteria for panic disorder at all trimester visits. Symptoms persisted for some patients even in the context of treatment with antipanic medications. Most subjects (n = 9) met DSM-III-R criteria at 1-3 months postpartum despite nearly uniform intensification of antipanic treatment. Although some women may experience diminished symptoms of panic during pregnancy, in this sample most continued to experience panic attacks and to require antipanic treatment to control symptoms.     

Severe neuromuscular complications possibly associated with amlodipine

OBJECTIVE: To document a case of severe, progressive myopathy, myalgias, arthralgias, and weakness possibly caused by amlodipine in a patient with benign essential hypertension. CASE SUMMARY: A 52-year-old white woman with asthma and newly diagnosed hypertension was initiated on zafirlukast therapy for asthma and amlodipine therapy for hypertension. Two months later, the patient reported severe, generalized muscle and joint pain, muscle stiffness, and weakness. The zafirlukast was discontinued without resolution of symptoms. Laboratory tests revealed an elevated C-reactive protein. The amlodipine dosage was increased. Her symptoms persisted and further laboratory tests revealed a positive anti-nuclear antibody screen, and negative single- and double-stranded DNA antibody tests. After another amlodipine dosage increase, the patient experienced a sudden onset of left-sided facial numbness, facial weakness, and a severe headache.The patient was admitted to rule out a possible cerebrovascular event or a metabolic neurologic process. Magnetic resonance imaging showed no abnormalities. The patient discontinued the amlodipine and reported complete resolution of the neurologic symptoms after 4 days. One month later, zafirlukast was reinitiated without a return of symptoms. CONCLUSIONS: Amlodipine was not initially suspected as a cause of these symptoms because these effects are not commonly associated with amlodipine therapy. However, due to the temporal relationship and progression of symptoms with increasing amlodipine dosage, drug-related causes were eventually explored. Review of the medical literature suggests myalgias and arthralgias may be adverse effects common to dihydropyridine calcium-channel antagonists.     

Estimating sequestered parasite population dynamics in cerebral malaria

Clinical investigation of malaria is hampered by the lack of a method for estimating the number of parasites that are sequestered in the tissues, for it is these parasites that are thought to be crucial to the pathogenesis of life-threatening complications such as cerebral malaria. We present a method of estimating this hidden population by using clinical observations of peripheral parasitemia combined with an age-structured mathematical model of the parasite erythrocyte cycle. Applying the model to data from 217 Gambian children undergoing treatment for cerebral malaria we conclude that although artemether clears parasitemia more rapidly than quinine, the clearance of sequestered parasites is similar for the two drugs. The estimated sequestered mass was found to be a more direct predictor of fatal outcome than clinically observed parasitemia. This method allows a sequential analysis of sequestered parasite population dynamics in children suffering from cerebral malaria, and the results offer a possible explanation for why artemether provides less advantage than might have been expected over quinine in reducing mortality despite its rapid effect on circulating parasites.