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Biomedical subjects

M Alexander

Publications and source records attributed to M Alexander.

At least 19 recordsLinked to original sources

Epidemiology of the post-polio syndrome.

A late-onset syndrome, consisting of muscle weakness, muscle pain, and unaccustomed fatigue, has been reported with increasing frequency among former poliomyelitis patients. A population-based cohort of poliomyelitis patients from Allegheny County, Pennsylvania, was traced and surveyed to estimate the prevalence and incidence and to identify determinants of the post-polio syndrome. A questionnaire validated in clinical examinations of 40 cohort members was used in the survey. The prevalence of the post-polio syndrome was 28.5% of all paralytic cases (95% confidence interval 24.4-32.6). The risk of post-polio syndrome was significantly higher among patients who sustained substantial permanent impairment after polio and among females. The incidence did not vary with age at acute onset, acute severity, or level of physical activity after recovery. The strongest determinant of post-polio syndrome onset was the length of the interval following the acute illness, with incidence peaking at 30-34 years. Of all cases of post-polio syndrome, 79% reported no major change in impairment status since onset. This study demonstrates that poliomyelitis patients are not equally susceptible to post-polio syndrome within the interval of 30-40 years after the original illness. For syndrome cases, the onset was associated with new neuromuscular symptoms and functional changes but not with major new impairment.

Acute Disease

Effect of chymotrypsin on human cholecystokinin release: use of clostripain in the validation of a new radioimmunoassay.

We have developed and validated a new radioimmunoassay for cholecystokinin. In order to establish that the antiserum binds large and small forms of CCK to an equal extent, we used the microbial enzyme clostripain, which cleaves large forms of CCK yielding CCK 8. Cleavage by clostripain of synthetic and purified forms of CCK, and CCK extracted at from human jejunum and CCK in human plasma was found not to affect immunoactivity, indicating that the antiserum reacts similarly with all forms of CCK. There is controversy over whether intraduodenal trypsin inhibits release of CCK in man. We used our radioimmunoassay to investigate whether chymotrypsin, rather than trypsin, could be the major mediator of negative feedback control of CCK release. Six normal subjects received an intraduodenal infusion of L-phenylalanine and L-tryptophan on two occasions, with the addition of either 1 g/l bovine chymotrypsin or 1 g/l albumin. Plasma CCK concentrations rose in response to the amino acid infusion, but were not affected by the addition of chymotrypsin, indicating that this enzyme is not a mediator of CCK feedback regulation in man.

Antibody Specificity

Hospital records as a data source for occupational disease surveillance: a feasibility study.

To assess the feasibility of using hospital records for occupational disease surveillance and to evaluate the quality of the industry/occupation (I/O) information available in these records, the computer file of all discharge diagnoses from a large health maintenance organization during 1985 was reviewed. The frequencies of discharge diagnoses previously listed as Sentinel Health Events (Occupational), or SHE (O), were calculated and three possible SHE(O) diagnoses--lung cancer, bladder cancer, and toxic hepatitis--were selected for further review. Outpatient charts of patients discharged for each diagnosis were abstracted with regard to I/O information and the discharged patients were interviewed by telephone to obtain a lifetime occupational history. The accuracy of the I/O information obtained from the hospital chart was compared to that obtained by patient interview by number of digits matched on standard classification codes. The frequencies of matches for occupation and industry were greater for "usual" than for "last" categories with both cancer diagnoses, but were similar for "usual" and "last" categories with toxic hepatitis. To assess the proportion of each possible SHE(O) diagnosis that was related to workplace exposures, the I/O information obtained by interview was rated in a blinded fashion by an experienced occupational medicine physician. The highest probability ratings for work-relatedness were noted for lung cancer, primarily due to asbestos exposure. The results of this study suggest that hospital records can be used to identify possible SHE(O); if adequate I/O information is available, then work-relatedness can be assessed. However, the accuracy of I/O obtained from hospital charts is relatively low. The efficient and accurate collection of I/O information from hospital records will require the use of a simple, easily coded instrument to be routinely administered on admission.

Asbestos

Malaria therapy in 452 patients, with special reference to the use of quinine.

We investigated the efficacy and toxic potential of antimalarial therapy regimens in 452 malaria patients treated between 1980 and 1990. Drug regimens in 330 non-immune travellers were compared with those of 122 semi-immunes with acute malaria; 71% patients acquired their infection in tropical Africa, and the 288 Plasmodium falciparum infections were the most prevalent species. Because of increasing drug resistance or toxicity of chloroquine, pyrimethamine-sulfadoxine and even mefloquine, quinine proved to be the most effective antimalarial against P. falciparum and the only one which did not lead to recrudescences. These occurred in 10% patients after chloroquine and 6% after mefloquine. Cinchonism occurred in 25% of those treated with quinine, but it was fully reversible and never necessitated withdrawal of the drug. We conclude that quinine is highly effective in the treatment of P. falciparum infection and is mandatory if the clinical condition requires a fast-acting blood schizonticide, in cases of hyper-parasitaemia and if multi-drug resistance occurs; its use should not be restricted by reversible side-effects such as cinchonism.

Adolescent

Benzodiazepines for acute pain in children.

When pediatric pain is refractory and unresponsive to appropriate use of analgesic agents, there might be additional physical or psychologic dimensions of the pain that are not addressed by the analgesics. In addition to appropriate analgesic therapy, the psychologic needs of the child should be directly addressed and appropriate adjunctive physical modalities employed. Although benzodiazepines lack direct analgesic effects, they can reduce the distress associated with acute pain states by decreasing anxiety, insomnia, and muscle spasms that can be associated with acute pain. Intermediate or long-acting benzodiazepines in modest doses can be useful adjunctive agents when used short term for the treatment of selected acute pain complaints. In the highly distressed school-age child or adolescent with pain complaints relatively unresponsive to appropriate care, judicious use of benzodiazepines is worthy of consideration.

Acute Disease

Bringing parents into school clinics: parent attitudes toward school clinics and contraception.

Prior to implementing a change in school clinic policy to allow dispensing of contraceptives, parents of school-based clinic (SBC) enrollees were surveyed regarding attitudes toward clinic quality of care, desired services, and contraceptive distribution. Telephone interviews were conducted with a systematic sample of 262 parents who normally are in charge of the adolescent's health care. Parental opinion was felt to be crucial in shaping Baltimore SBC contraception policy. Parents overwhelmingly endorsed current clinic services including family planning for sexually active teens, annual physicals, and drug and alcohol counseling. Most parents rated the SBC as excellent (25%) or very good (36%), although a substantial minority found it difficult to rate the clinics (27%, "don't know"). Parents with prior verbal contact (45%) were more likely to rate the clinic as excellent (35% versus 16%) and less likely to respond "don't know" (13% versus 38%, p less than 0.001). Parent attitudes toward contraception was context specific: 63% endorsed and 27-30% opposed prescribing and dispensing. If a boy (or girl) was already having sex, 76% (or 75%) of parents supported and 14% (or 17%) opposed providing birth control pills or condoms. With parental permission, 93% supported contraception and only 3% were opposed. No differences were found by age, race, gender, or grade of student. Prior verbal communication with the clinic did not affect parent attitudes toward contraception. Consideration of parent attitudes was critical to changing SBC contraceptive dispensing policy in Baltimore. Contraceptive distribution, after counseling and necessary medical care, was initiated in September 1990. The parent and community response has been very supportive.

Adolescent

Sleep and cardiorespiratory characteristics of infant victims of sudden death: a prospective case-control study.

We studied the polygraphic sleep recordings of 30 infants who eventually died of sudden infant death syndrome (SIDS) and those of 60 matched control infants. All records were extracted from 20,750 sleep studies collected prospectively in 10 sleep laboratories. Of the 30 future SIDS victims, 5 were siblings of SIDS victims and 9 were studied after an apparent life-threatening event. For each SIDS victim, two normal control infants were matched for sex, gestational age, postnatal age and weight at birth. The future SIDS infants were reported to have more frequent episodes of regurgitations after feeding (p = 0.01) and profuse sweating during sleep (p = 0.01) than the control subjects. Only two polysomnographic variables characterized the future SIDS infants. Compared to control subjects, the SIDS infants moved less during sleep (p = 0.04) and had significantly more frequent obstructed breathing events. Obstructive and mixed apneas were seen in 23 of 30 future SIDS victims, but in only 9 of 60 control subjects (p = 0.01). The obstructed and mixed apneas lasted longer in the SIDS than in the control infants (p = 0.01) but did not exceed 15 seconds. The obstructed breaths occurred mainly in rapid eye movement sleep (78% of the events) and were accompanied by drops in heart rates to 68 beats per minute and in SaO2 levels to 75%. The present report adds further indirect evidence for a possible sleep-related impairment of respiratory control in some infants who eventually died of SIDS.

Case-Control Studies

Normal uptake in a gravid uterus on Tc-99m DTPA imaging.

A 17-year-old female kidney transplant patient was admitted to the hospital with a fever and right lower quadrant pain. Although she was 14 weeks' pregnant, renal DTPA imaging was performed because graft rejection was suspected. The study revealed fetal uptake of DTPA medial to the transplanted kidney. This has not been previously reported. Uptake in a normal uterus has been described using Tc-99m pertechnetate, Tc-99m glucoheptonate, and Tc-99m MDP. It is essential to recognize uptake in the gravid uterus and to differentiate it from uptake secondary to a pathologic entity.

Adolescent

Infection control.

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Acquired Immunodeficiency Syndrome

The prognostic significance of race and survival from laryngeal carcinoma.

Surveillance, Epidemiology, and End Results (SEER) program data suggest that blacks with laryngeal carcinoma have a significantly lower 5-year survival rate than whites. Most of this difference persists despite adjustment for "crude stage." To evaluate possible factors contributing to this residual survival deficit, 190 white and 23 black patients treated at the Martinez Veterans Administration Hospital between 1968 and 1988 were studied. The independent impact of race on survival rate was analyzed with respect to various prognostic factors including treatment delay, elapsed time (diagnosis to treatment), age, stage, cancer subsites, and type of therapy. No independent prognostic significance could be attributed to race. The differences noted in SEER data probably reflect a tendency for the use of crude stage to underestimate the impact of prognostic groups within the categories of "local" and "regional" disease, the independent prognostic significance of subsites (glottic versus supraglottic), and the variable distribution of these subsites in different populations. This study suggests that when stage, subsite, and quality of care are adequately considered, survival from laryngeal cancer in blacks is comparable to that of whites.

Adult

[Tuberculosis of the larynx, oral cavity and pharynx].

A 44-year-old man, a heavy smoker over many years, complained of hoarseness for 8 weeks with weight loss and dysphagia. Malignant tumour of the pharynx was suspected. Examination revealed a swelling of the right upper lip, tumorous changes in the right buccal mucosa, about 6 x 6 cm in size, as well as enlargement of the cervical lymph-nodes. Microlaryngoscopy revealed a three-level tumour of the entire side of the right larynx. Histological examination of biopsies of the right false and true vocal cords as well as the buccal mucosa demonstrated numerous, partly caseous epithelioid granulomas with Langhans giant cells. Ziehl-Neelsen staining showed acid-fast rods. Combined tuberculostatic treatment with isoniazid, rifampicin, ethambutol and pyrazinamide achieved regression of all signs and symptoms within two months. This case emphasizes the need for including laryngeal tuberculosis in the differential diagnosis of seemingly malignant laryngeal tumours.

Adult

Clinical evaluation of the efficacy and safety of noberastine, a new H1 antagonist, in seasonal allergic rhinitis: a placebo-controlled, dose-response study.

Noberastine (NOB), a new histamine H1 antagonist, has potent and specific peripheral antihistaminic activity. To evaluate the efficacy and safety of NOB in ragweed seasonal allergic rhinitis, 250 eligible patients were randomized to one of four parallel, double-blind treatment groups: NOB, 10, 20, and 30 mg, or placebo, each administered once daily for 3 weeks. Rescue medication was prohibited. Efficacy parameters included global response rate (percentage of responders), physician visit, patient-diary symptom scores, and onset of action. Efficacy analyses used alpha = 0.0167 (adjusted for multiple comparisons). Efficacy parameters demonstrated universal superiority of NOB therapy over placebo therapy with statistical significance achieved frequently; no statistically or clinically significant separation was demonstrated among NOB-treated groups. Global-response rates for all active-treatment groups (range, 62.7% to 71.1%) were statistically significantly greater than rates for the placebo-treated group (39.6%). Median time to first relief of symptoms was within 2 to 4 hours for NOB-treated groups versus 72 hours for the placebo-treated group. No significant abnormalities in safety parameters were ascribed to NOB treatment. Incidence and severity of adverse experiences of NOB-treated groups were comparable in incidence and severity to placebo treatment. NOB treatment did not appear to cause weight gain or sedation. Once-daily NOB, 10, 20, and 30 mg, is equally and highly effective and safe in the symptomatic management of seasonal allergic rhinitis compared to placebo.

Adolescent

Effect of sodium chloride on transport of bacteria in a saturated aquifer material.

Determinations were made of the influence of NaCl concentration, cell density, and flow velocity on the transport of Pseudomonas sp. strain KL2 through columns of aquifer sand under saturated conditions. A pulse-type boundary condition was used. The experiments were conducted by using 0.3-m-long Plexiglas columns with an internal diameter of 0.05 m. When a 1-h pulse of a 0.01 M NaCl solution containing 10(8) cells per ml was added at a flow rate of 10(-4) m s-1, the bacterial density in the effluent never exceeded 2.2% of the density of cells added, and only 1.5% of the bacteria passed through the aquifer material. In contrast, when the bacteria were applied in distilled water, the relative cell density in the effluent approached 100%, and 60% of the bacteria were transported through the aquifer solids. Under these conditions, the breakthrough of Pseudomonas sp. strain KL2 was slower than chloride. When the flow rate was 2.0 x 10(-4) m s-1, the cell density in the effluent reached 7.3% of that added in 0.01 M NaCl solution, but only 3.9% of the bacteria were transported through the aquifer particles. On the other hand, the density in the effluent approached 100% of that added in deionized water, and 77% of the added bacteria were recovered. When the density of added cells was 10(9) cells per ml at a flow rate of 10(-4) m s-1, the densities in the effluent reached 70 and 100% of those added in salt solution and deionized water, respectively, and 44 and 57% of the bacteria were transported through the aquifer solids.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Movement

Sexual behavior in male rhesus monkeys elicited by electrical stimulation of preoptic and hypothalamic areas.

Electrical stimulation of the preoptic area, lateral hypothalamus or dorsomedial nucleus of the hypothalamus (DMH) has produced sexual behavioral responses in 11 male rhesus monkeys. At a short latency following the onset of each train of stimulation, the stimulated males would mount estrogen-treated, receptive females. Quantitative measures of the elicited sexual behavior, in 4 males, were applied to describe differences between the effect of preoptic and DMH stimulation on male sexual performance. As compared to spontaneous sexual activity, stimulation of the DMH produced mounts of longer duration, with more thrusts per mount, higher thrusting rates and a greater number of ejaculations per test session; refractory periods between successive ejaculatory episodes were shortened as a result of stimulation-induced mounting behavior. Preoptic stimulation also induced mounts of longer than normal duration characterized by a slightly increased number of thrusts per mount. In contrast to DMH stimulus effects, however, thrusting rate was decreased significantly by preoptic stimulation and ejaculation did not occur even after multiple stimulus-induced mounts. Penile erections were elicited by stimulation of the anterior hypothalamus, ventromedial nucleus and the posterior hypothalamus in socially isolated or restrained males; however, stimulation of these same sites was ineffective for provoking sexual behavioral responses when tests were performed while the males were paired with receptive females.

Animals