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Biomedical subjects

D A Hoffman

Publications and source records attributed to D A Hoffman.

At least 19 recordsLinked to original sources
PubMed1997

Slow recovery from inactivation of Na+ channels underlies the activity-dependent attenuation of dendritic action potentials in hippocampal CA1 pyramidal neurons.

Na+ action potentials propagate into the dendrites of pyramidal neurons driving an influx of Ca2+ that seems to be important for associative synaptic plasticity. During repetitive (10-50 Hz) firing, dendritic action potentials display a marked and prolonged voltage-dependent decrease in amplitude. Such a decrease is not apparent in somatic action potentials. We investigated the mechanisms of the different activity dependence of somatic and dendritic action potentials in CA1 pyramidal neurons of adult rats using whole-cell and cell-attached patch-clamp methods. There were three main findings. First, dendritic Na+ currents decreased in amplitude when repeatedly activated by brief (2 msec) depolarizations. Recovery was slow and voltage-dependent. Second, Na+ currents decreased much less in somatic than in dendritic patches. Third, although K+ currents remained constant during trains, K+ currents were necessary for dendritic action potential amplitude to decrease in whole-cell experiments. These results suggest that regional differences in Na+ and K+ channels determine the differences in the activity dependence of somatic and dendritic action potential amplitudes.

Action Potentials↗
PubMed1997

K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons.

Pyramidal neurons receive tens of thousands of synaptic inputs on their dendrites. The dendrites dynamically alter the strengths of these synapses and coordinate them to produce an output in ways that are not well understood. Surprisingly, there turns out to be a very high density of transient A-type potassium ion channels in dendrites of hippocampal CA1 pyramidal neurons. These channels prevent initiation of an action potential in the dendrites, limit the back-propagation of action potentials into the dendrites, and reduce excitatory synaptic events. The channels act to prevent large, rapid dendritic depolarizations, thereby regulating orthograde and retrograde propagation of dendritic potentials.

Action Potentials↗
PubMed1991

Simple method for the determination of inorganic sulfate in human serum and urine using single-column ion chromatography.

A single-column ion chromatographic assay with conductivity detection was developed to determine inorganic sulfate concentrations in human plasma and urine samples. Plasma samples were ultrafiltered to remove proteins. Plasma ultrafiltrate and urine samples were diluted prior to injection onto the anion-exchange column. The described method is simple, fast, sensitive and reproducible and was used to study the effect of subchronic administration of acetaminophen on the plasma concentrations and urinary excretion of inorganic sulfate in healthy volunteers.

Acetaminophen↗
PubMed1990

Circadian rhythm of serum sulfate levels in man and acetaminophen pharmacokinetics.

The circadian variation of serum inorganic sulfate levels was studied in healthy volunteers. The effect of subchronic acetaminophen administration (650 mg q.i.d. for 4 days) on serum inorganic sulfate levels was investigated and the possible role of fluctuating serum inorganic sulfate levels on the pharmacokinetics of acetaminophen was evaluated. During a 24 h cycle, serum inorganic sulfate levels were lowest in the morning (11.00 h) and typically increased in the afternoon to reach a maximum in the early evening (19.00 h). Average 24 h serum concentrations were 360 microM and the difference between minimum and maximum levels was on average 25.8%. Subchronic administration of acetaminophen (650 mg q.i.d. for 4 days) significantly reduced serum inorganic sulfate levels to a 24 h average of 253 microM. The circadian rhythm, however, was not affected and the difference between minimum (12.00 h) and maximum (18.50 h) serum concentrations was 31.3%. Subchronic acetaminophen administration lead to a significant decrease in the renal excretion (-51%) and renal clearance (-33%) of inorganic sulfate. No significant differences were found in the disposition kinetics of acetaminophen and its glucuronide and sulfate conjugates during two consecutive dosing intervals (08.00-14.00 h, 14.00-20.00 h) on Day 4 of the acetaminophen regimen.

Acetaminophen↗
PubMed1989

Breast cancer in women with scoliosis exposed to multiple diagnostic x rays.

Although exposure to ionizing radiation is a recognized risk factor for breast cancer, the potential hazard from low-dose, fractionated exposures during early breast development has not been thoroughly evaluated. Women with scoliosis represent a valuable population for studying this issue because they are exposed to multiple diagnostic x rays during childhood and adolescence, times when the breast may be highly sensitive to the carcinogenic effects of radiation. A study was conducted of 1,030 women with scoliosis who were seen at four Minneapolis area medical facilities between 1935 and 1965. The average age at diagnosis was 12.3 years; 60% of the women had idiopathic scoliosis. Individual x-ray films were counted and the number per patient ranged from 0 to 618 films (mean, 41.5). On average, the x-ray exposures were given over an 8.7-year period. Ninety percent of the women were located, of whom over 92% responded to a mail questionnaire or telephone interview. The average period of observation was 26 years. Overall, 11 cases of breast cancer were reported, compared with six expected (standardized incidence ratio = 1.82, 90% confidence interval = 1.0-3.0). Excess risk increased with time since exposure and was highest among those followed for more than 30 years (standardized incidence ratio = 2.4). Risk also increased with the number of x rays and with the estimated radiation dose to the breast (mean, 13 rad). These data suggest that frequent exposure to low-level diagnostic radiation during childhood or adolescence may increase the risk of breast cancer.

Adult↗
PubMed1988

Reproductive outcomes in scoliosis patients.

In a retrospective cohort study of 1,409 persons diagnosed with scoliosis between 1927 and 1965 in Minneapolis and St. Paul, Minnesota, mailed questionnaires were obtained for 846 white women. Six hundred and eight (72%) of these women had ever been pregnant, and they reported a total of 1,733 pregnancies and 1,413 livebirths. Adverse outcomes among the pregnancies and livebirths of the 608 women were reported, including spontaneous abortion, stillbirth, low birth weight, prematurity, congenital anomalies, and complications of pregnancy or delivery. Rates of these events for the scoliosis patients were compared with corresponding expected rates. Comparison of the overall rates suggested that the scoliosis patients had more premature births than expected, but their rates of other adverse reproductive events did not differ from expected.

Adult↗
PubMed1985

Second cancer following cutaneous melanoma and cancers of the brain, thyroid, connective tissue, bone, and eye in Connecticut, 1935-82.

The risk of second primary cancers developing was evaluated in individuals with 6 rare tumors in Connecticut between 1935 and 1982. Small but significant excesses of all second cancers occurred in patients with cutaneous melanoma (42%), and cancers of the brain (59%), thyroid (49%), connective tissue (23%), bone (66%), and eye (40%). In individuals with cutaneous melanoma, the highest risks were for subsequent cutaneous melanomas [relative risk (RR) = 8.5] that persisted throughout all intervals of observation. The risk for second melanomas was higher in persons under age 40, consistent with a heritable component. Connective tissue tumors and breast cancers also occurred in excess. Among patients with brain cancer, an increase of melanoma was observed that may represent an underlying neural crest abnormality, although no excess of brain cancer was seen after melanoma. Reciprocal increases of bone cancer after connective tissue cancer and connective tissue cancer after bone cancer point to shared risk factors, such as high dose radiotherapy or genetic susceptibility states. An anticipated high risk of osteogenic sarcoma following Ewing's sarcoma was not seen. An excess of breast cancer (RR = 1.9) after thyroid cancer indicates common etiologic factors. Expected excesses of bilateral retinoblastoma and bone cancer after retinoblastoma were seen. Tumors commonly treated with alkylating agents or nitrosoureas (melanoma, brain, connective tissue) showed slightly elevated risks of acute nonlymphocytic leukemia. Prostate cancer was frequently found to be in excess, but this is likely an artifact due to ascertainment bias.

Bone Neoplasms↗
PubMed1984

Breast cancer in hypothyroid women using thyroid supplements.

The risk of breast cancer associated with thyroid supplementation for iatrogenic hypothyroidism was investigated in women treated for hyperthyroidism at the Mayo Clinic, Rochester, Minn. One or more years after the diagnosis of hypothyroidism, there were 47 cases of breast cancer observed among 1,665 women compared with 52.9 cases expected, a ratio of observed to expected cases (standardized incidence ratio [SIR]) of 0.9. There was also no breast cancer excess among women who remained euthyroid (SIR = 1.0). Breast cancer risks were not influenced by various factors associated with the management of hyperthyroidism or subsequent hypothyroidism. No increased risk was observed in hypothyroid women categorized by breast cancer risk factors except for women who reported a previous breast biopsy, an excess also observed among euthyroid patients. The results of this study indicate that use of thyroid supplements does not increase the risk of breast cancer developing.

Adult↗
PubMed1984

Relationship of thyroid disease and use of thyroid supplements to breast cancer risk.

An interview study of 1362 breast cancer cases and 1250 controls identified through a multi-center screening program allowed evaluation of effects of thyroid disease and supplementation on breast cancer risk. A previous diagnosis of treated thyroid disease was not associated with an excess risk (RR = 1.0), nor were any specific diagnoses, including hypothyroidism, hyperthyroidism, or goiter. Although based on limited numbers, women with untreated hypothyroidism or goiter had a significantly reduced risk of breast cancer (RR = 0.3, 95% CI 0.1-0.7). Thyroid supplementation for non-disease reasons (primarily weight loss and fertility problems) was associated with a slight elevation in breast cancer risk (RR = 1.2, 95% CI 0.9-1.7), but patterns of risk by duration and latency generally failed to provide evidence of causality. Elevated risks were noted among women who received thyroid medications for fertility problems (RR = 4.2) and among those with a family history of breast cancer (RR = 2.6) or a late age at first childbirth (RR = 2.4), possibly indicating an hormonal interaction.

Adult↗
PubMed1984

Multiple primary breast and thyroid cancer.

The occurrence of breast and thyroid multiple primary cancers was evaluated using data from the Connecticut Tumor Registry. The study population consisted of 1618 women with primary thyroid cancer and 39,194 women with primary breast cancer diagnosed between 1935 and 1978. Thirty-four thyroid cancer patients subsequently developed breast cancer and 24 breast cancer patients later had thyroid cancer. A significantly elevated risk of thyroid cancer following breast cancer (SIR = 1.68) and breast cancer following thyroid cancer (SIR = 1.89) was demonstrated. The finding was even more notable when compared with the risks obtained for other sites. The elevated risk was particularly evident in women under 40 years of age at time of diagnosis of the first cancer. Analysis by histologic type revealed that the highest risk of second primary breast cancer was found among patients with follicular or mixed papillary-follicular thyroid cancer. Women under age 40 with follicular carcinoma had a 10-fold risk of developing breast cancer (4 observed, 0.4 expected). An enhanced risk of second primary tumours was evident for the entire period after treatment of the first primary, although it was highest within one year after diagnosis of the first primary. This may be due to the close medical surveillance of cancer patients which would increase early diagnosis of second tumours. Our findings suggest that breast and thyroid cancer may share common aetiologic features.

Adult↗
PubMed1983

Profound hyperglycemia and metabolic acidosis after verapamil overdose.

Verapamil, a potent calcium antagonist, possesses varied systemic effects, including smooth muscle relaxation leading to both peripheral and coronary artery vasodilation, slowed atrioventricular nodal conduction and decreased insulin release from the pancreatic B cells. Reports concerning the effects of acute intoxication with verapamil are scarce. A case is presented of a 22 year old woman who developed profound hyperglycemia and metabolic acidosis after the inadvertent overdose of thirty 80 mg tablets (2,400 mg) of verapamil. This case illustrates the need for physicians to be aware of verapamil's inhibitory effects on insulin release and to exercise special care when prescribing verapamil in patients with preexisting diabetes mellitus.

Acidosis↗
PubMed1983

Second primary malignancies following salivary gland cancers.

Four hundred and fifteen males and 367 females who had invasive malignant tumours of the salivary glands as their first cancer diagnosed in Connecticut between 1935 and 1978 were identified and followed 2342 and 2868 person-years respectively. Overall a slight excess of second primary cancers (relative risk 1.35) was observed. Significant excesses were noted for respiratory cancers in males (relative risk 2.8) and for ovarian cancer (relative risk 5.3) but not breast cancer (relative risk 1.3) in women. Possible reasons for excesses at these sites are discussed, but it seems most likely they are related to small number variation.

Adenocarcinoma↗
PubMed1983

Breast cancer following iodine-131 therapy for hyperthyroidism.

A retrospective cohort study of women treated for hyperthyroidism at the Mayo Clinic between 1946 and 1964 was conducted to determine if 1,005 women treated with iodine-131 (131I) were at increased risk of breast cancer compared with 2,141 women traced, and a response (death certificate or questionnaire) was received for 99% of the traced women. The average duration of follow-up was 15 years for the 131I-treated women and 21 years for women treated surgically. No increased risk of breast cancer was observed in the 131I-treated women (adjusted relative risk = 0.8). No patterns were found of increased breast cancer risk by age at first treatment, by time since treatment, or by total exposure to 131I. Failure to detect an increased risk of breast cancer in the 131I-treated women was attributed to the moderately low doses from 131I therapy and the relatively small number of exposed women. The study also failed to find any increased risk of breast cancer associated with hyperthyroidism.

Adult↗
PubMed1982

Cancer incidence following treatment of hyperthyroidism.

A retrospective cohort study of women treated for hyperthyroidism at the Mayo Clinic was conducted to evaluate the risk of cancer according to type of therapy. One or more years after the start of treatment, there were 105 cases of cancer observed among 1005 women treated with radioiodine (131I) and 247 cases among 2141 women treated with surgery. No difference was observed between the two study groups for total cancer incidence (RR = 1.0), breast cancer (RR = 0.8), or leukaemia (RR = 0.6). Although based on small numbers of cases, an elevated risk of cancer was observed in organs that concentrate 131I (salivary glands, digestive tract, kidney and bladder) (RR = 1.8). While the findings are suggestive, they indicate the need for larger surveys to evaluate the carcinogenic potential of 131I.

Age Factors↗
PubMed1982

Mortality in women treated for hyperthyroidism.

To evaluate the late effects of exposure to radioiodine (131I), a retrospective cohort study was conducted of women treated for hyperthyroidism at the Mayo Clinic, Rochester, Minnesota, from 1946 through 1964. Cause of death was determined in 1005 women treated with 131I and in 2141 women surgically treated. No increased risk of total mortality was observed for the 131I-treated women (relative risk = 1.0). There were no increased risks for the major causes of mortality (cancer, cardiovascular-renal disease or cerebrovascular lesions) in the 131I-treated women; in addition, there were no increased risks for site-specific cancer mortality. Several hypotheses are presented to suggest reasons for the lack of an association between 131I exposure and increased cancer mortality.

Adult↗