The Salivary Mycobiome Contains 2 Ecologically Distinct Mycotypes.

A broad range of fungi has been detected in molecular surveys of the oral mycobiome. However, knowledge is still lacking on interindividual variability of these communities and the ecologic and clinical significance of oral fungal commensals. In this cross-sectional study, we use internal transcribed spacer 1 amplicon sequencing to evaluate the salivary mycobiome in 59 subjects, 36 of whom were scheduled to receive cancer chemotherapy. Analysis of the broad population structure of fungal communities in the whole cohort identified 2 well-demarcated genus-level community types (mycotypes), with Candida and Malassezia as the main taxa driving cluster partitioning. The Candida mycotype had lower diversity than the Malassezia mycotype and was positively correlated with cancer and steroid use in these subjects, smoking, caries, utilizing a removable prosthesis, and plaque index. Mycotypes were also associated with metabolically distinct bacteria indicative of divergent oral environments, with aciduric species enriched in the Candida mycotype and inflammophilic bacteria increased in the Malassezia mycotype. Similar to their fungal counterparts, coexisting bacterial communities associated with the Candida mycotype showed lower diversity than those associated with the Malassezia mycotype, suggesting that common environmental pressures affected bacteria and fungi. Mycotypes were also seen in an independent cohort of 24 subjects, in which cultivation revealed Malassezia as viable oral mycobiome members, although the low-abundance Malassezia sympodialis was the only Malassezia species recovered. There was a high degree of concordance between the molecular detection and cultivability of Candida, while cultivation showed low sensitivity for detection of the Malassezia mycotype. Overall, our work provides insights into the oral mycobiome landscape, revealing 2 community classes with apparently distinct ecologic constraints and specific associations with coexisting bacteria and clinical parameters. The utility of mycotypes as biomarkers for oral diseases warrants further study.

Continuous i.v. infusion versus multiple bolus doses of metoclopramide for prevention of cisplatin-induced emesis.

Continuous infusion of metoclopramide was compared with bolus dosing in a randomized, double-blind study in 27 patients receiving cisplatin therapy. Hospitalized patients receiving their first course of cisplatin (120 mg/sq m administered i.v. over four hours) were randomized to receive either bolus doses or a continuous infusion of metoclopramide. In the infusion group (14 patients), a loading dose of metoclopramide 3 mg/kg (total body weight) as the hydrochloride salt was infused over one hour immediately before the administration of cisplatin, followed by a continuous infusion of metoclopramide 0.5 mg/kg/hr (as the hydrochloride salt) for 12 hours. Each patient received a total metoclopramide dose of 9 mg/kg over 13 hours. These patients also received five bolus doses of 5% dextrose injection (as placebo) over 15 minutes, with the first dose given one hour before the cisplatin and four more doses at two-hour intervals. In the bolus-dose group (13 patients), metoclopramide 2 mg/kg as the hydrochloride salt was added to each of the bolus doses, while the continuous infusion was a placebo of 5% dextrose injection. All patients also received dexamethasone 10 mg i.v. and diphenhydramine hydrochloride 50 mg i.v. Patients were monitored for 24 hours after initiation of metoclopramide administration for number of emesis episodes and for adverse effects. In the infusion group, 11 of 14 (79%) patients had two or fewer episodes of emesis. In the bolus group, 10 of 13 (77%) had two or fewer vomiting episodes. Mild sedation occurred in both the infusion (79%) and bolus-dose (77%) groups. Despite the use of diphenhydramine, extrapyramidal reactions were seen in one bolus-dose patient and two infusion patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of administration rate on cisplatin-induced emesis.

In an attempt to determine the influence of administration time on cisplatin-induced emesis, 20 adults previously untreated with cisplatin were enrolled into this double-blind study. Twenty patients were randomly assigned to receive high-dose cisplatin (greater than 100 mg/m2) either by a one-hour infusion or by an eight-hour infusion. All patients received antiemetic therapy with metoclopramide 2 mg/kg intravenously one-half hour before cisplatin administration, and 1 1/2, 3 1/2, 5 1/2, and 8 1/2 hours after cisplatin administration. Patients in the eight-hour infusion group experienced significantly fewer emesis episodes than did patients in the one-hour infusion group. The median of emesis episodes in the eight-hour group was one (range, 0 to 2) and in the one-hour group was three (range, 0 to 8). In patients receiving high-dose cisplatin plus metoclopramide, increasing the administration time from one hour to eight hours resulted in a small but significant decrease in emesis episodes. The cisplatin infusion rate should be considered as a variable in cisplatin-antiemetic trials.

Male breast cancer following repeated fluoroscopy.

A man with cancer of the breast following repeated fluoroscopy for pulmonary tuberculosis is described.

Antiemetic efficacy of prochlorperazine, haloperidol, and droperidol in cisplatin-induced emesis.

The antiemetic efficacy of haloperidol, droperidol, and prochlorperazine in preventing cisplatin-induced emesis was evaluated. Twenty-seven patients receiving 51 courses of cisplatin chemotherapy randomly received antiemetic treatment with prochlorperazine (6 mg/sq m), droperidol (1 mg/sq m), or haloperidol (1 mg/sq m) in a double-blind crossover study. Antiemetics were given by intramuscular injection one hour before beginning cisplatin and every three hours thereafter for a total of six doses. The number of emetic episodes, volume of emesis, and duration of the emetic episodes were monitored by oncology nurses. There were no significant differences in the median number of emetic episodes among antiemetic treatments: 3.5 for prochlorperazine, 4.0 for haloperidol, and 3.0 for droperidol. There were also no significant differences among the antiemetics in the median volume of emesis or the median duration of the emetic episodes. At the doses used in this study, the antiemetic efficacy of prochlorperazine, droperidol, and haloperidol appear to be comparable for patients receiving cisplatin chemotherapy.

Prophylaxis of oral candidiasis with clotrimazole troches.

Oropharyngeal candidiasis is frequently a complication of patients with altered immune states. Clotrimazole troches are effective in the treatment of Candida and were evaluated in this study in a prophylaxis regimen. Patients with malignant neoplasms who were receiving chemotherapy and renal transplant recipients who were receiving immunosuppressives were randomized to receive either clotrimazole (10 mg) or placebo troches three times a day in a prospective, double-blinded study. Eighty-four patients were randomized into the study, 18 patients with leukemia, 19 patients with malignant neoplasms, and 47 patients with renal transplants. Among all patients, thrush developed in 57% while receiving placebo compared with 13% while receiving clotrimazole prophylaxis. Prophylaxis showed significant benefit for the renal transplant recipients and for patients with solid malignant neoplasms, but not for the leukemic patients. Clotrimazole troches are effective in preventing oral candidiasis in a select group of patients.

Preliminary trial of combination therapy with adriamycin and radiation in sarcomas and other malignant tumors.

Based on reports of synergism between adriamycin and radiation therapy in experimental systems, a trial was initiated testing this combination in 53 adult patients with various advanced malignancies, especially sarcomas. Since studies have suggested as selective sensitization of hypoxic cells when this drug is given prior to radiation, an injection of low-dose adriamycin was given 90 min before radiation. This treatment was repeated every 7 days. The combination was most effective in the 30 patients with soft-tissue sarcomas, with 62% of these patients having partial or complete responses. Responses were less good in patients with gastric adenocarcinoma or with other tumors. The toxicity of the combined treatment was moderate. Further trials of this combination are warranted.

Angioimmunoblastic lymphadenopathy: clinical spectrum of disease.

The clinical features of 13 patients with angioimmunoblastic lymphadenopathy were analyzed to determine prognostic factors and response to therapy. Eleven patients presented with sudden onset of fever, weight loss, generalized lymphadenopathy, and hepatosplenomegaly. Laboratory features included autoimmune hemolytic anemia and polyclonal hypergammaglobulinemia. Pulmonary involvement was seen in six cases and skin rash in four. Two patients had localized lymphadenopathy without systemic symptoms. Both are alive at 5.5 and 2.5 years, respectively, after diagnosis, although the latter patient has required intermittent prednisone for recurrent lymphadenopathy. An additional patient is alive on treatment for months following diagnosis. The remaining ten have died, nine of sepsis and one of cerebral hemorrhage. The immunosuppression and myelosuppression of combination chemotherapy may have hastened their deaths. An individualized, conservative treatment approach is recommended.

Basal cell carcinoma in black patients.

Fourteen cases of basal cell carcinoma occurring in North American black patients were reviewed. The majority of the lesions were asymptomatic, hyperpigmented, translucent nodules and were correctly diagnosed as being basal cell carcinomas prior to biopsy. All of the lesions except one arose in the sun-exposed areas of the head and neck, indicating that basal cell carcinoma in blacks, as in whites, is related to exposure to ultraviolet light. Microscopic examination revealed changes characteristic of basal cell carcinoma. The response to therapy in our patients was good. There appear to be no histologic or clinical differences in the basal cell carcinomas that arise in black and white patients.

A phase of I trial of 4'-epi-Adriamycin.

4'-epi-adriamycin was administered intravenously on an every-3-week schedule to 34 patients with advanced malignant tumors. Patients were treated at five dosage levels, ranging from 40 mg/m2 to 100 mg/m2. Hematologic toxicity was dose limiting. No cardiac, renal, or hepatic toxicity was observed; there were no drug-related deaths. Partial alopecia developed in all patients receiving a cumulative dose of 200 mg/m2; mild nausea and vomiting occurred in 13 patients. Although major therapeutic responses were not seen in this phase I trial, 2 of 15 patients with objectively measurable disease showed minor responses; 7 patients had stabilization of previously progressing cancer for 3 to 5+ months. A dose of 85 mg/m2 of epi-Adriamycin every 3 weeks seems an appropriate initial dose for phase II studies in patients having a performance status of 70 or higher. A starting dose of 70 mg/m2 is recommended for patients having a lower performance status.