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T L Smith

Publications and source records attributed to T L Smith.

At least 91 records · Page 5Linked to original sources
PubMed1999

Emergence of vancomycin resistance in Staphylococcus aureus. Glycopeptide-Intermediate Staphylococcus aureus Working Group.

BACKGROUND: Since the emergence of methicillin-resistant Staphylococcus aureus, the glycopeptide vancomycin has been the only uniformly effective treatment for staphylococcal infections. In 1997, two infections due to S. aureus with reduced susceptibility to vancomycin were identified in the United States. METHODS: We investigated the two patients with infections due to S. aureus with intermediate resistance to glycopeptides, as defined by a minimal inhibitory concentration of vancomycin of 8 to 16 microg per milliliter. To assess the carriage and transmission of these strains of S. aureus, we cultured samples from the patients and their contacts and evaluated the isolates. RESULTS: The first patient was a 59-year-old man in Michigan with diabetes mellitus and chronic renal failure. Peritonitis due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus peritonitis associated with dialysis. The removal of the peritoneal catheter plus treatment with rifampin and trimethoprim-sulfamethoxazole eradicated the infection. The second patient was a 66-year-old man with diabetes in New Jersey. A bloodstream infection due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus bacteremia. This infection was eradicated with vancomycin, gentamicin, and rifampin. Both patients died. The glycopeptide-intermediate S. aureus isolates differed by two bands on pulsed-field gel electrophoresis. On electron microscopy, the isolates from the infected patients had thicker extracellular matrixes than control methicillin-resistant S. aureus isolates. No carriage was documented among 177 contacts of the two patients. CONCLUSIONS: The emergence of S. aureus with intermediate resistance to glycopeptides emphasizes the importance of the prudent use of antibiotics, the laboratory capacity to identify resistant strains, and the use of infection-control precautions to prevent transmission.

Aged↗
PubMed1999

Hodgkin's disease with lymphocyte predominance: long-term results based on current histopathologic criteria.

PURPOSE: To define the disease course, therapeutic strategies, patterns and rates of relapse and causes of death for patients with Hodgkin's disease with lymphocyte predominance (LPHD) and to assess prognostic factors including nodular and diffuse histologic patterns. PATIENTS AND METHODS: The records of all previously untreated patients with LPHD who received initial treatment at the University of Texas M. D. Anderson Cancer Center (UTMDACC) from 1960 through 1992 were reviewed. Clinical and histopathologic characteristics, specifically nodular and diffuse LPHD, and treatment groups were assessed by overall and relapse-free survival, patterns of relapse, and causes of death. RESULTS: Of 70 patients, 58 (83%) had nodular LPHD and 12 (17%) had a diffuse pattern: clinical characteristics were similar between the two subtypes. The median age of all patients was 25 years, 79% were male, 96% presented with stage I or II disease and 93% were free of B symptoms. Laparotomy (23 patients) failed to upstage any patient with a negative lymphogram. With a median follow-up of 12.3 years for alive patients, 19 (27%) patients have relapsed. All 3 relapses among the patients with diffuse subtype occurred within 3 years while 9 of 16 relapses occurred after 5 years with nodular subtype. However, we did not detect any statistically significant difference in relapse free survival or survival between the subtypes in our patient population. There was some suggestion that patients aged 40 and older experienced shorter survival; no other pretreatment characteristics were noted to be associated with relapse free survival or survival. Though there were no relapses within the radiation fields, no effect of extent of radiation therapy on relapse rate was observed. Thirteen (19%) patients have died, 6 (8.6%) of whom succumbed to LPHD. Two patients developed diffuse large cell lymphoma. CONCLUSIONS: Patients with LPHD usually present with localized and asymptomatic disease. Laparotomy is unnecessary if the lymphogram is negative. Nodular histology occurred in the majority of patients. Though all relapses from diffuse subtype occurred within 3 years in contrast to some late relapses observed for nodular subtype, there was no statistically significant difference in relapse free survival or survival between the subtypes. The extent of irradiation had no effect on relapse free survival or survival. We could not find any evidence that LPHD should be treated any different from the classical Hodgkin's disease at this point despite suggestions that it be classified as a non-Hodgkin's B-cell lymphoma.

Adolescent↗
PubMed1999

Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy: a reference.

BACKGROUND: The authors report results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with doxorubicin-containing combination chemotherapy at a single institution; this report is meant to serve as a reliable reference for single-arm studies of newer therapies in this patient population. METHODS: Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast carcinoma were evaluated. RESULTS: The response rate was 65.0% (95% confidence interval [CI]: 62.5-67.3%), complete response (CR) rate was 16.6% (95% CI: 14.8-18.6%), and partial response (PR) rate was 48.5% (95% CI: 46.0-50.9%). Median progression free survival (PFS) was 11.5 months (95% CI: 10.9-12.3 months) and median overall survival (OS) was 21.3 months (95% CI: 20.3-22.7 months). Survival correlated with response to therapy; median PFS and OS were 22.4 and 41.8 months, respectively, for the patients who achieved CR (n=263) and 14 and 24.6 months, respectively, for PR patients (n=766). The median OS of patients who had progressive disease during chemotherapy was 3.8 months. The response rate, PFS and OS correlated with number of organs involved and especially with tumor burden. Patients with hormone receptor-positive tumors had a similar response rate to that of patients with hormone receptor negative tumors but had significantly longer PFS (medians of 14.3 and 8.7 months, respectively) and OS (medians of 28.6 and 18.1 months, respectively). CONCLUSIONS: In patients with metastatic breast carcinoma, doxorubicin-containing chemotherapy had a response rate of 65% and a CR rate of 16.6%. PFS and OS were 11.5 months and 21.3 months, respectively, for all responders and 22.4 months and 41.8 months, respectively, for those who had CR.

Adult↗
PubMed1999

Morphology of the complex laryngeal gland in the Atlantic bottlenose dolphin, Tursiops truncatus.

A complex lymphoepithelial gland is a constant feature in the larynx of Atlantic bottlenose dolphins, Tursiops truncatus, based on study of 56 animals. Larynges were removed from fresh, non-decomposed beach-stranded animals for gross examination and histological sampling. A large lymphoepithelial gland occurs in the rostro-ventral mucosa of the larynx, overlying the cricoid cartilage. It presents as a well-defined, elevated, and heavily trabeculated area. Histological examination reveals a pseudostratified columnar epithelium which branches into the underlying submucosa. The epithelial-lined folds and crypts thus formed are surrounded by aggregations of lymphocytes, which infiltrate this epithelium. Mucous glands are often associated with these lymphoid aggregations. The histological appearance of the laryngeal gland is remarkably similar to the palatine, or dorsal oropharyngeal tonsils, of T. truncatus. It may be analogous to the nasopharyngeal adenoid of terrestrial animals. Age-related involution of the laryngeal gland is not as obvious with increasing animal age (or length) as it is in other mucosa-associated lymphoid tissue. The distribution of this gland among cetaceans is not yet known. We have observed it in individuals of every species we have studied, including Lagenodelphis hosei, Stenella coeruleoalba, Stenella attenuata, Globicephala macrorhynchus, Steno bredanensis, Physeter catodon, Pseudorca crassidens, Mesoplodon europaeus, and Kogia breviceps.

Animals↗
PubMed1999

Anatomic and physiologic evaluation of upper extremity ischemia.

This study assessed the accuracy of arteriography and laser Doppler perfusion imaging (LDPI) as predictors of digital ischemia and correlated upper extremity symptoms, function, and nutritional flow with arteriographic and laser Doppler assessments. Multiple-level occlusive disease was documented in 25 hands (23 patients) by arteriography. LDPI demonstrated one or more hypoperfused digits in 17 hands. Patient questionnaires were used to assess upper extremity symptoms, pain, cold sensitivity, and function. Spearman correlation coefficients indicated that arteriography is a poor indicator of nutritional perfusion as measured by LDPI. Neither arteriography or laser Doppler perfusion imaging served as an indicator of the severity of cold intolerance. However, upper extremity symptoms and functional status correlated with both laser Doppler measurements and the level of cold sensitivity. Laser Doppler perfusion imaging and arteriographic analysis provide complimentary data in the evaluation of upper extremity ischemia.

Adolescent↗
PubMed1999

[Microcirculation of striated muscle in closed soft tissue injury: effect on tissue perfusion, inflammatory cellular response and mechanisms of cryotherapy. A study in rat by means of laser Doppler flow-measurements and intravital microscopy].

The authors investigated the effects of closed soft tissue injury (CSTI) and cryotherapy on microvascular perfusion by means of laser Doppler flowmetry. In a different protocol interactions between leukocytes and the microvascular endothelium of skeletal muscle, which are first steps in local inflammatory response were documented in an intravital microscopy model. Rats were chronically instrumented with dorsal skinfold chambers. Leukocyte rolling and adherence in postcapillary venules of striated muscle before and after standardized muscle contusion (group T: n = 6), cryotherapy following muscle contusion (TK: n = 6) or sham contusion (group N: n = 6) were quantitated prospectively and in random order using intravital microscopy. Tissue perfusion was assessed by laser Doppler flowmetry in the microvasculature of the flap over a period of 96 hours following CSTI (group T: n = 8), cryotherapy following CSTI (group TK: n = 8), sham trauma (group N: n = 8, control 1), or cryotherapy following sham trauma (group K: n = 8, control 2). 300 minutes after trauma the number of rolling and adherent leukocytes in striated muscle microvasculature was significantly reduced by cryotherapy. We found an acute effect of cryotherapy on perfusion of traumatized tissue (reduction of perfusion around 25 %). However, there was no long-term effect (96 hours evaluation) on microvascular perfusion of cryotherapy either in the presence or absence of CSTI. The effectiveness of ice application in reducing edema in striated muscle following contusion may be due in part to a reduction of the leukocyte/endothelial interactions accompanying CSTI.

Animals↗
PubMed1999

Reliability of the Tone Assessment Scale and the modified Ashworth scale as clinical tools for assessing poststroke spasticity.

OBJECTIVES: To establish reliability of the Tone Assessment Scale and modified Ashworth scale in acute stroke patients. SETTING: A North Liverpool university hospital. PATIENTS: Eighteen men and 14 women admitted with acute stroke and still in hospital at the study start date (median age, 74 yrs; median Barthel score, 8). MAIN OUTCOME MEASURES: The modified Ashworth scale and the Tone Assessment Scale. STUDY DESIGN: The 32 patients were examined with both scales on the same occasion by two raters (interrater comparison) and on two occasions by one rater (intrarater comparison). RESULTS: The reliability of the modified Ashworth scale was very good (kappa = .84 for interrater and .83 for intrarater comparisons). The reliability of the Tone Assessment Scale was not as strong as the modified Ashworth scale, with marked variability in the assessment of posture (kappa = .22 to .50 for interrater and .29 to .55 for intrarater comparisons) and associated reaction (kappa/kappaW = -.05 to .79 for interrater and .19 to .83 for intrarater comparisons). However, those aspects of the Tone Assessment Scale that addressed response to passive movement and that are scored similarly to the modified Ashworth scale showed good to very good interrater reliability (kappaW = .79 to .92) and good to very good intrarater reliability (kappaW = .72 to .86), except for the question related to movement at the ankle where agreement was only moderate (kappaW = .59). CONCLUSIONS: The modified Ashworth scale is reliable. The section of the Tone Assessment Scale relating to response to passive movement is reliable at various joints, except the ankle. It may assist in studies on the prevalence of spasticity after stroke and the relationship between tone and function. Further development of a measure of spasticity at the ankle is required. The Tone Assessment Scale is not reliable for measuring posture and associated reactions.

Aged↗
PubMed1999

Antimicrobial resistance in Staphylococcus aureus.

Recognized since 1883 as a common cause of infection, Staphylococcus aureus' preantimicrobial-era bacteremia mortality rate was 82%. The mortality of that era threatens to return as evidence of growing vancomycin resistance undermines the utility of vancomycin therapy. Successful treatment of S. aureus infections requires knowledge of its antimicrobial resistance capacity.

Anti-Bacterial Agents↗
PubMed1999

Non-insulin-dependent diabetic microangiopathy in the inner ear.

UNLABELLED: Hearing loss has long been associated with diabetes mellitus. Microangiopathy, associated with thickening of the basement membranes of small vessels, has been implicated as a major source of multiple system organ disease. OBJECTIVE: This study was designed to evaluate changes in basement membrane thickness in the inner ear of laboratory animals suffering from non-insulin-dependent diabetes mellitus (NIDDM) with, and without, exposure to moderate intensity noise exposure in an attempt to extrapolate the same disease process in humans. DESIGN: Spontaneously hypertensive-corpulent non-insulin-dependent rats (SHR/N-cp) were selected as a genetic model for the above study. Both lean and obese rats were used in this study. A genetically similar control group of animals (LA/N-cp) were used as controls. These animals express both the lean and obese phenotypes, but they lack the NIDDM gene. Forty-eight animals in each group were sacrificed at the end of the study. The cochleas were dissected and fixed. The basement membrane of the stria vascularis was examined using transmission electron microscopy. SETTING: This study was a laboratory-based, standard animal study. MAIN OUTCOME: This study was designed to show microangiography of the inner ear as related to NIDDM with, and without, obesity and noise exposure. RESULTS/CONCLUSIONS: NIDDM alone does not cause statistically significant basement membrane thickening; however, NIDDM in combination with obesity and/or noise exposure did show significant thickening and the combination of all three showed the greatest thickening. NIDDM appeared to be the greatest contributing factor.

Animals↗
PubMed1999

Relapse after complete response to anthracycline-based combination chemotherapy in metastatic breast cancer.

In this study we examined the clinical characteristics of relapse before and after complete clinical response (CR) to anthracycline-based combination chemotherapy in metastatic breast cancer (MBC). Our goal was to determine whether similar clinical trends could be observed during first relapse and relapse after CR. Two hundred and sixty-three patients with MBC were identified who had achieved CR after anthracycline-based combination chemotherapy for first recurrence. From this group, 226 patients had relapse after CR after a minimum follow-up of 13 years. Clinical features of their disease at first relapse and after progression from CR (second relapse) were examined, including disease-free interval (DFI) from diagnosis until first relapse, sites of recurrence, response to subsequent therapy, and survival after progression from CR. There was a significant correlation between duration of CR and survival after progression from CR. Patients who relapsed < 12 months after achieving CR had a median survival of 8.8 months after second relapse, whereas those who relapsed beyond 3 years had a median survival of 21.5 months (p = 0.0034). Neither the duration of CR nor length of survival after second relapse was related to the length of initial DFI. Patients with a short duration of CR (< 12 months) more often experienced second recurrences at multiple sites and in visceral organs (62% and 75%, respectively) than did patients with prolonged CR (> 36 months) (27% and 45%, respectively, p < 0.001). The anatomic location of metastatic disease at the time of first and second relapses was similar within a CR duration group but different among the groups. Short CR duration was associated with more frequent recurrence at visceral sites and also with chemotherapy-resistant second relapse. In conclusion, prolonged CR is associated with long survival after second relapse; however, neither CR duration nor survival after second relapse is related to the length of initial DFI. This suggests that chemotherapy, when it induces CR, may change the pace of disease progression. The tissue pattern of recurrence appears to be similar between first and second relapse, suggesting that the cellular predilection for metastatic sites has been preserved.

Antibiotics, Antineoplastic↗
PubMed1999

Morphology of the lymphoid organs of the bottlenose dolphin, Tursiops truncatus.

The anatomy of the lymphoid organs was studied during the course of detailed dissections of 50 beach-stranded bottlenose dolphins, Tursiops truncatus. Constant lymph nodes occur in 4 groups, based on their location and structure. These groups are somatic, including nodes of the cervical region and pelvic recess; lung-associated, included marginal, diaphragmatic and hilar nodes; visceral, including the mesenteric, pancreatic, pericolic and porta hepatis nodes; and aortic arch nodes. Lymphatic drainage of the lung is primarily to the marginal and diaphragmatic nodes. The mesenteric node mass is well-endowed with capsular and trabecular smooth muscle, and a network of muscle fascicles within the organ implies an important contractile function in the circulation of lymph. In addition to constant nodes, occasionally nodes are found in relation to the thoracic aorta, the kidney, and under the scapula. Gut-associated structures include dorsal and ventral oropharyngeal tonsils, mucosal aggregates in the straight segment of the intestine (colon) and anal tonsils; this gut-associated lymphoid tissue tends to involute with age, being greatly reduced by puberty. Formed lymphoid organs include the thymus and the spleen, the latter being relatively small in relation to body size. None of these structures is unique among cetaceans, but the anal tonsils are particularly well developed in T. truncatus. The lymphoid aggregates in the colon resemble the arrangement in the vermiform appendix, which is lacking in most cetaceans, and may have functions analogous to that organ.

Animals↗
PubMed1999

Radiofrequency tissue ablation of the inferior turbinates using a thermocouple feedback electrode.

OBJECTIVE: The objective of this clinical trial was to assess the safety and efficacy of radiofrequency (RF) tissue ablation of the inferior turbinates in the treatment of nasal obstruction using an RF energy delivery system with a thermocouple feedback electrode. METHODS: A prospective, nonrandomized study of 11 patients (mean age, 47+/-12 y) with chronic nasal obstruction was conducted. Using patient-based visual analogue scales (VAS), symptom parameters were assessed. These included degree of nasal obstruction, frequency of nasal obstruction, and pain. Physician assessment of nasal obstruction was also collected by the principal investigator. Follow-up was conducted at 24 hours, 1 week, 4 weeks, 8 weeks, and 1 year. ANOVA was carried out to determine statistically significant differences in the data. Data were fit to a regression model, and confidence intervals were determined from a 95% confidence level. RESULTS: In patient-assessed degree of nasal obstruction, statistical significance was seen among baseline and 4 weeks, 8 weeks, and 1 year (P<.001, P<.0001, and P<.0008, respectively). There was no difference between 8 weeks and 1 year (P<.15). The data appeared to follow an exponential decay to a constant value. The pretreatment baseline average degree of obstruction was 7.5+/-0.5 on a scale of 0 to 10. The degree of obstruction after 8 weeks was 2.7+/-0.6. The time constant for this change was 21 days to reach 90% of the final value. At 1 year, degree of obstruction was 3.3+/-0.7. For frequency of nasal obstruction, statistical significance was seen among baseline and 4 weeks, 8 weeks, and 1 year (P<.0001, P<.0001, and P<.0001, respectively). There was no difference between 8 weeks and 1 year (P<.15). The pretreatment baseline average frequency of obstruction was 7.8+/-0.5. The remaining frequency of obstruction after 8 weeks was 2.9+/-0.6. The time constant was 18 days. At 1 year, frequency of obstruction was 3.3+/-0.6. Physician assessment of nasal obstruction revealed statistical significance among baseline and 4 weeks, and baseline and 8 weeks (P<.0055 and P<.0056, respectively). There was no difference between 4 weeks and 8 weeks (P<.24). The average initial obstruction was 83%+/-4%. The remaining obstruction after 8 weeks was 58% +/-5%. The time constant was 14 days. Mild pain was reported by 55% of patients during the procedure; the remaining 45% reported no pain. Only one patient required pain medication consisting of acetaminophen after the procedure. There were no significant complications. CONCLUSIONS: Degree and frequency of nasal obstruction, as reported by patients, decreased following RF tissue ablation of the inferior turbinates. This improvement in symptoms was still evident after 1 year (P<.001). Physician assessment of obstruction also correlated with patient reports for the initial 8-week study period. The procedure was safe and well tolerated. Thermocouples within the active electrode provided additional feedback to the operating surgeon allowing the use of relatively lower tissue temperatures, power, and energy as compared with traditional techniques. These results support the need for continued research to evaluate this modality as a treatment for chronic nasal obstruction.

Adult↗
PubMed1999

Direct medical charges associated with myocardial infarction in patients with and without diabetes.

OBJECTIVES: This study was designed to measure the direct medical charges for patients with and without diabetes who experience myocardial infarction. METHODS: We completed a retrospective cohort analysis (from the third-party payer perspective) to determine the total direct medical charges (eg, hospitalizations, outpatient visits, pharmacy, and emergency room visits) incurred by an inner city sample of 293 patients during the 12 months following myocardial infarction during the period from January 1993 through February 1997. RESULTS: The 87 patients with diabetes had a higher per patient total direct medical charge (inclusive of initial hospitalization) compared to the 206 patients without diabetes ($18,577 versus $26,414) and approximately $3000 more per person year of observation. Hospitalizations (initial and during the follow-up period) accounted for 88% of the total direct medical charges. The mean charge for the initial hospitalization was higher for patients with diabetes ($12,730 versus $15,394). In a subset, the mean charge per cardiovascular-related hospitalization that occurred during the follow-up period was also higher for patients with diabetes ($6344 versus $9648). CONCLUSIONS: Consistent with what we expected, patients with diabetes incurred higher total direct medical charges as a result of and following myocardial infarction. These data can be used in future cost-effectiveness evaluations for therapies developed to treat patients with diabetes who experience myocardial infarction or for therapies designed to reduce the risk of macrovascular complications associated with diabetes.

Adult↗
PubMed1999

Evaluation of a novel, anti-herpes simplex virus compound, acyclovir elaidate (P-4010), in the female guinea pig model of genital herpes.

The antiviral effect of acyclovir elaidate in the female guinea pig model of genital herpes was investigated in a series of experiments. The antiherpesvirus effects of this novel compound, 9-(2'-[trans-9"-octadecenoyloxyl]ethoxymethyl)guanine (code no. P-4010), were studied in both primary and recurrent genital herpes in the female guinea pig, following oral gavage or intraperitoneal injection, with different formulations of the compound, and in comparison with acyclovir (ACV) or penciclovir (PCV). The results indicate that compound P-4010 has a greater capability than either ACV or PCV in reducing the clinical symptoms of primary genital herpes induced following the inoculation of herpes simplex virus type 2 (HSV-2) intravaginally into guinea pigs. In addition, the administration of P-4010 twice daily over a 10-day period by the intraperitoneal route (15 to 40 mg/kg of body weight/day) or by oral gavage (50 to 200 mg/kg/day), commencing 4 h subsequent to intravaginal HSV-2 infection, resulted in a degree of reduction in the incidence and severity of spontaneous, recurrent genital herpes in these animals. The findings are discussed in the light of the value and relevance of the female guinea pig model of genital herpes for the assessment of anti-herpes simplex virus compounds.

Acyclovir↗
PubMed1999

Clinical implications for four drugs of the DSM-IV distinction between substance dependence with and without a physiological component.

OBJECTIVE: The DSM-IV work group asked researchers and clinicians to subtype substance dependent individuals according to the presence or absence of physiological symptoms. A recent report from the Collaborative Study on the Genetics of Alcoholism demonstrated that among alcohol-dependent men and women, a history of tolerance or withdrawal was associated with a more severe clinical course, especially for individuals with histories of alcohol withdrawal. This article evaluates similar distinctions among subjects in the collaborative study who were dependent on marijuana, cocaine, amphetamines, or opiates. METHOD: Structured interviews gathered information from 1,457 individuals with a lifetime diagnosis of marijuana dependence, 1,262 with histories of cocaine dependence, 647 with amphetamine dependence, and 368 subjects with opiate dependence. For each drug, the clinical course was compared for subjects whose dependence included a history of withdrawal (group 1), those dependent on each drug who denied withdrawal but reported tolerance (group 2), and those who denied both tolerance and withdrawal (group 3). RESULTS: The proportion of dependent individuals who denied tolerance or withdrawal (group 3) ranged from 30% for marijuana to 4% for opiates. For each substance, individuals in groups 1 and 2 evidenced more severe substance-related problems and at least a trend for greater intensities of exposure to the drug; those reporting withdrawal (group 1) showed the greatest intensity of problems. CONCLUSIONS: The designation of dependence in the context of tolerance or withdrawal identifies individuals with more severe clinical histories. These results support the importance of the designation of a physiological component to dependence, especially for people who have experienced a withdrawal syndrome.

Adult↗
PubMed1999

Treatment of Philadelphia chromosome-positive early chronic phase chronic myelogenous leukemia with daily doses of interferon alpha and low-dose cytarabine.

PURPOSE: To evaluate the efficacy of the combination of interferon alpha (IFN-alpha) and daily low-dose cytarabine (ara-C) in the treatment of patients with early chronic-phase chronic myelogenous leukemia (CML) (within 1 year of diagnosis). Improving the degree of hematologic and cytogenetic response in patients with Philadelphia chromosome (Ph)-positive CML may improve prognosis. Both IFN-alpha and ara-C induce cytogenetic responses as single-agent therapy in CML. PATIENTS AND METHODS: One hundred forty patients with Ph-positive early chronic-phase CML received subcutaneous injections of IFN-alpha 5 megaunits/m2 daily and ara-C 10 mg daily. Their median age was 46 years; 53% had good-risk disease, 33% had intermediate-risk disease, and 14% had poor-risk disease. Their results were compared with those of patients receiving IFN-alpha with or without intermittent ara-C (7 days/mo). RESULTS: A complete hematologic response (CHR) was achieved in 92% of patients. A cytogenetic response was seen in 74%: it was major in 50% (Ph-positive < 35%) and complete in 31% (Ph-positive 0%). With a median follow-up of 42 months, the 4-year estimated survival rote was 70% (95% confidence interval, 61% to 79%). Significant side effects included fatigue (43%; grade 3/4, 11%), weight loss (19%; grade 3/4, 11%), muscle and bone aches (20%; grade 3/4, 7%), oral ulcers (4%), diarrhea (6%), and neurologic changes (27%, grade 3/4, 6%). The median dose of IFN-alpha was 3.7 megaunits/m2 daily, mainly because of reductions for myelosuppression (70% of cases); the median ara-C dose was 7.5 mg daily. Prognostic risk groups were predictive for response to the IFN-alpha plus ara-C combination. The incidence of CHR was higher with IFN-alpha plus daily ara-C compared with IFN-alpha plus intermittent ara-C and IFN-alpha alone (no ara-C) (92% v 84% v 80%, P = .01), as were the incidences of cytogenetic response (74% v 73% v 58%; P = .003) and major cytogenetic response (50% v 38% v 38%; P = .06). The median time to achievement of major cytogenetic response was significantly shorter than that for previous IFN-alpha regimens (7 v 10 v 12 months; P < .01). However, with the present follow-up, the survival and time to blastic transformation were similar. CONCLUSION: The combination of IFN-alpha plus daily low-dose ara-C seems to be promising for the treatment of CML. High rates of CHR and cytogenetic response were observed with acceptable toxicity and a lower daily dose of IFN-alpha compared with our previous studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer.

PURPOSE: To compare prospectively the antitumor activity of single-agent paclitaxel to the three-drug combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC) as neoadjuvant therapy in patients with operable breast cancer. PATIENTS AND METHODS: Patients with T1-3N0-1M0 disease were randomized to receive either paclitaxel (250 mg/m(2)) as 24-hour infusion or FAC in standard doses at every-3-week intervals. Each patient was treated with four cycles of preoperative chemotherapy. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after four cycles of induction chemotherapy. RESULTS: A total of 174 patients were registered, and 87 were randomized to each arm of the study. Clinical response, ie, complete and partial responses, was similar in both arms of the study. Three patients in the FAC arm and one patient in the paclitaxel subgroup had progressive disease. The extent of residual disease by intent-to-treat analysis at the time of surgery was similar between the two arms of the study. CONCLUSION: The results of this prospective study demonstrated that single-agent paclitaxel as neoadjuvant therapy has significant antitumor activity, and this was clinically comparable to FAC. Similar fractions of patients had clinical complete and partial responses, and very few patients had no response to either therapy. The value of alternate non-cross-resistant therapies as used in this protocol on the clinical course of this disease would require longer follow-up.

Adult↗