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Biomedical subjects

A Braverman

Publications and source records attributed to A Braverman.

16 recordsLinked to original sources
PubMed2002

Predilection of hemolytic anemia-associated leg ulcers for the medial malleolus.

BACKGROUND: Ischemic ulcers are usually found above the lateral, and venous stasis ulcers at the medial malleoli. Leg ulcers occur in at least 25% of sickle cell disease (SSD) patients in clinic populations, usually in the malleolar region. The function of the large leg veins in most SSD patients is unimpaired. PATIENTS AND METHODS: We determined leg ulcer location in 41 sickle cell anemia (SS), and 4 sickle-beta 0 thalassemic patients with longstanding chronic and/or recurrent leg ulceration, and reviewed published reports of leg ulcers in hereditary spherocytosis and thalassemias. RESULTS: Of the 57 legs of the 45 SSD patients with only 1 ulcer, 42 (74%) were medial and 15 lateral. The difference was significant (p < 0.001). Of patients with only a single ulcer, 22 were medial and 4 lateral. Of 15 reported patients with leg ulcers related to spherocytosis or thalassemia, 20/24 (83%) ulcers were medial. CONCLUSIONS: The medial malleoli are the most common site of leg ulceration in SSD and in other chronic hemolytic anemias. This suggests that stasis may play a role in the leg ulceration associated with chronic hemolytic anemia.

Adult↗
PubMed1999

M2 receptors in genito-urinary smooth muscle pathology.

In vitro bladder contractions in response to cumulative carbachol doses were measured in the presence of selective muscarinic antagonists from rats which had their major pelvic ganglion bilaterally removed (denervation, DEN) or from rats in which the spinal cord was injured (SCI) via compression. DEN induced both hypertrophy (505+/-51 mg bladder weight) and a supersensitivity of the bladders to carbachol (EC50=0.7+/-0.1 uM). Some of the SCI rats regained the ability to void spontaneously (SPV). The bladders of these animals weighed 184+/-17 mg, significantly less than the bladders of non voiding rats (NV, 644+/-92 mg). The potency of carbachol was greater in bladder strips from NV SCI animals (EC50=0.54+/-0.1 uM) than either bladder strips from SPV SCI (EC50=0.93+/-0.3 microM), DEN or control (EC50=1.2+/-0.1 microM) animals. Antagonist affinities in control bladders for antagonism of carbachol induced contractions were consistent with M3 mediated contractions. Antagonist affinities in DEN bladders for 4-diphenlacetoxy-N-methylpiperidine methiodide (4-DAMP, 8.5) and para fluoro hexahydrosilodifenidol (p-F-HHSiD, 6.6); were consistent with M2 mediated contractions, although the methoctramine affinity (6.5) was consistent with M3 mediated contractions. p-F-HHSiD inhibited carbachol induced contraction with an affinity consistent with M2 receptors in bladders from NV SCI (pKb=6.4) animals and M3 receptors in bladders from SPV SCI animals (pKb=7.9). Subtype selective immunoprecipitation of muscarinic receptors revealed an increase in total and an increase in M2 receptor density with no change in M3 receptor density in bladders from DEN and NV SCI animals compared to normal or sham operated controls. M3 receptor density was lower in bladders from SPV SCI animals while the M2 receptor density was not different from control. This increase in M2 receptor density is consistent with the change in affinity of the antagonists for inhibition of carbachol induced contractions and may indicate that M2 receptors or a combination of M2 and M3 receptors directly mediate smooth muscle contraction in bladders from DEN and NV SCI rats.

Animals↗
PubMed1989

Determining the optimal dosage regimen for H2-receptor antagonist therapy--a dose validation approach.

A large number of clinical studies have been performed to establish the safety and efficacy of H2-receptor antagonist therapy. Few if any of these studies have attempted to address the rationale for the dosage and/or dosage regimens being studied. This study is the first large-scale clinical trial, the purpose of which is to validate the chosen regimen and to address the issue of an optimal therapy for a specific patient population. A regimen of a single nightly dosage is generally acknowledged to offer the potential for improved patient compliance. Furthermore, recent research had suggested that suppression of nocturnal acid secretion is all that is required to heal duodenal ulcers. Hence such a regimen offered the potential for an effective lowered dosage of cimetidine with minimal interference with gastric physiology, increased safety and substantial efficacy. This multicentre, double-blind, placebo-controlled trial therefore evaluated a 4-week course of single night-time dosage of cimetidine. After 4 weeks of treatment the cumulative, endoscopically proven, ulcer healing rate with an 800 mg regimen was 73%, which was statistically higher and significantly superior to the 41% healing seen with placebo (P less than 0.001). The 400 mg nocte dosage regimen of cimetidine normally used as maintenance therapy was significantly inferior to the 800 mg nocte regimen (P = 0.01), and increasing the dosage to 1600 mg nocte for 4 weeks failed to provide a significant improvement in healing over the 800 mg nocte regimen. This 800 mg nocte regimen provided rapid pain relief, with 75% of the patients being free of night-time pain and 65% free of day-time pain, by the end of the first week. The 400 mg 'maintenance dosage' was unable to provide this degree of rapid, complete and early relief to patients with a duodenal ulcer. Furthermore, increasing the dosage to 1600 mg nocte failed to increase the level of early pain relief significantly, perhaps because the extensive response of duodenal ulcer patients to the 800 mg nocte regimen leaves little room for improvement. Based both on the early symptom relief and the ulcer healing rate during 4 weeks of treatment, it is concluded that an 800 mg night-time dosage of cimetidine may be an optimal regimen for many duodenal ulcer patients, particularly those who in the physician's opinion will benefit from a once-daily regimen.

Adolescent↗
PubMed1988

Patient compliance with aggressive multimodal therapy in locally advanced breast cancer.

This study of compliance was performed to determine whether a medically indigent population with breast carcinoma that has been neglected is an appropriate group for inclusion in an aggressive combined treatment program. After incisional biopsy, 28 locally advanced breast cancer (LABC) patients received two cycles of cytoxan, Adriamycin, 5-Fluorouracil, and tamoxifen (CAFT) followed by a simple mastectomy and level I axillary dissection. After surgery, patients received four additional cycles of CAFT alternating with three cycles of 15 Gy to the chest wall and regional lymphatics. Compliance was defined as overall compliance, the percentage of patients completing the protocol as described; and appointment compliance, the ratio between treatments or appointments attended versus those scheduled. Overall compliance was 75% (21 of 28 patients). The total number of appointments scheduled was 1054 (mean, 37 +/- 2), and the total attended was 965 (mean, 34 +/- 3), giving an appointment compliance rate of 91.7%. Compliance did not vary significantly with age, marital status, nationality, the presence of complications, or delay to diagnosis. Compliance did decrease significantly with time. There was 100% overall compliance at 2 months, 82% at 6 months, and 75% at 1 year. We conclude that although our patients had neglected their disease and were medically indigent, they were highly motivated patients once in therapy. This suggests that complex treatment regimens are feasible as well as effective for the treatment of LABC.

Adult↗
PubMed1987

Treatment of advanced bladder carcinoma with irradiation and concomitant 5-fluorouracil infusion.

Nineteen patients with locally advanced bladder cancer were treated with irradiation and concomitant 5-fluorouracil intravenous infusion with or without bolus mitomycin. Eighteen of the 19 patients were evaluated for local response. Eleven of the 18 patients (61%) obtained a complete local response within 3 to 6 months. An additional five patients (28%) showed tumor regression to a superficial state controlled by local transurethral resection and intravesical chemotherapy making the overall local clearance rate 16/18 (89%). The remaining two patients (11%) required salvage cystectomy for persistent disease and presently show no evidence of disease. Nine patients have died. Two patients died of intercurrent disease, six patients died of metastatic disease, and one patient who died from regional disease showed no evidence of local bladder tumor at the time of death. Berkson-Gage life-table analysis yields an adjusted survival of 62.5% at 5 years. Late complications included five patients with hemorrhagic cystitis, two patients with a contracted bladder, and one patient with a hemorrhagic radiation proctitis.

Aged↗
PubMed1986

Multimodal therapy for locally advanced breast cancer.

Thirty-one women with stage III breast cancer were prospectively treated with two cycles of cyclophosphamide (Cytoxan), doxorubicin hydrochloride (Adriamycin), fluorouracil, and tamoxifen citrate followed by a simple mastectomy with level I axillary dissection. Postoperatively, four additional cycles of the combination chemotherapy alternating with three cycles of 1500 rad (15 Gy) to the chest wall and lymphatics were given. Seventy-seven percent of patients had a greater than 50% reduction in tumor size after the initial chemotherapy. No tumor size progressed during therapy, and a single patient remained inoperable. Pathologic findings revealed nine patients with only microscopic residual tumor. Nuclear vacuolization was present in 42.8% of tumor cells after chemotherapy vs 14.2% of cells before chemotherapy. The mean follow-up for the groups is 24.3 months. To date, nine patients have had recurrence with only one isolated local recurrence. This therapy is effective in reducing primary tumor size and allows a limited mastectomy to be done with minimal morbidity.

Adult↗
PubMed1986

Response of colo-rectal hepatic metastases to concomitant radiotherapy and intravenous infusion 5 fluorouracil.

Twenty-three patients with colo-rectal hepatic metastases were retrospectively reviewed after completing treatment with split course liver irradiation and continually infused concomitant intravenous 5-fluorouracil. Although no patient attained a complete response, an objective partial response was documented in 15 (Responders). The Responders had a median survival of 45 weeks whereas Non-responders had a median survival of 17 weeks. Patients with metastatic disease solely in the liver or those with a Karnofsky performance score (k.p.s) of over sixty, had a median survival of 49 weeks. Patients with multiple organ metastatic involvement had a median survival of 25 weeks and those with a Karnofsky with less than 60 had a median survival of 27 weeks. (p values of 0.006 and 0.03, respectively.) The overall survival of the group completing treatment was 30 weeks, and 19 patients (83%) achieved subjective palliation. The patients tolerated therapy well. There was minimal hematological toxicity; 3 patients developed a leucocyte count of less than 2000 and 1 developed a platelet count of 30,000. The palliation and prolongation of survival attained with minimal complications suggest that adjuvant liver irradiation with concomitant infusion 5-fluorouracil radiosensitization may be an option to offer patients identified to be at high risk of developing subclinical liver disease.

Adult↗
PubMed1986

The effect of single intravenous doses of cimetidine or ranitidine on gastric secretion.

Intravenous cimetidine, 300 mg or 400 mg, or ranitidine, 50 mg, was administered as a single dose to 36 volunteers in a randomized, crossover fashion. Aspirates of gastric juice were obtained after dosing, and the pH, titratable acidity, gastric fluid volume, and gastric acid output were determined from baseline through 71/2 hours for each subject. Each intervention significantly increased pH and suppressed hydrogen ion concentration, gastric fluid volume, and gastric acid output. Both the magnitudes of the changes when compared with baseline and the time of the mean maximum effects were similar in all three drug regimens. The effect of all three interventions on gastric fluid volume and gastric acid output diminished sharply after 6 hours. The data indicate that the gastric secretory response to all three interventions did not differ substantially.

Adolescent↗
PubMed1986

Total lymphoid irradiation in refractory systemic lupus erythematosus.

In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental.

Adult↗
PubMedDate not supplied

Accurate prediction of the amount of in situ tumor in palpable breast cancers by core needle biopsy: implications for neoadjuvant therapy.

BACKGROUND: Neoadjuvant chemotherapy facilitates breast conservation in stage II breast cancer patients, whose primary tumors are assumed to be invasive because they are palpable. However, chemotherapy may not be indicated in the minority of patients whose clinically T2 tumors are completely or predominantly in situ. Almost all previous studies of core needle biopsy in breast cancer have been concerned with nonpalpable, mammographically detected tumors, and none have evaluated its ability to quantitatively determine the amounts of in situ and invasive disease. METHODS: From September, 1992 to December, 1997, core needle biopsy was performed on all patients presenting to the Kings County Hospital Breast Clinic with palpable breast masses. Carcinoma was present in both core needle biopsy samples and surgical specimens subsequently obtained from 95 of 99 patients. Each specimen was evaluated for tumor type, histologic grade, and the amounts of in situ and invasive carcinoma it contained, and the results from surgical and core needle biopsy specimens from the same patients were then compared. RESULTS: The surgical specimens of 14 patients had completely or predominantly in situ disease. Completely or predominantly invasive disease was present in 67 specimens, and the remaining 14 had significant amounts of both. The high level of agreement between the amounts of in situ and invasive disease in core needle biopsy and surgical specimens is indicated by Pearson and intraclass correlation coefficients of 0.91 (P < .001 and < .00001, respectively). Tumor type was correctly predicted by core needle biopsy in each case. Variables among these patients, including primary tumor size, interval between biopsy and surgery, or administration of neoadjuvant systemic therapy, did not alter agreement between core needle biopsy and surgical specimens. CONCLUSIONS: Core needle biopsy can identify palpable breast tumors that are predominantly or completely in situ, and, thus, avoid unnecessary neoadjuvant chemotherapy. It also can demonstrate that a tumor is predominantly invasive, but cannot rule out small invasive foci. For that purpose, complete surgical excision of the tumor is required.

Biopsy, Needle↗