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Biomedical subjects

M Mumenthaler

Publications and source records attributed to M Mumenthaler.

At least 19 recordsLinked to original sources
PubMed1998

Effect of excipients on the stability and structure of lyophilized recombinant human growth hormone.

We have investigated the effect of mannitol, sorbitol, methyl alpha-D-mannopyranoside, lactose, trehalose, and cellobiose on the stability and structure of the pharmaceutical protein recombinant human growth hormone (rhGH) in the lyophilized state. All excipients afforded significant protection of the protein against aggregation, particularly at levels to potentially satisfy water-binding sites on the protein in the dried state (i.e., 131:1 excipient-to-protein molar ratio). At higher excipient-to-protein ratios, X-ray diffraction studies showed that mannitol and sorbitol were prone to crystallization and afforded somewhat less stabilization than at lower ratios where the excipient remained in the amorphous, protein-containing phase. The secondary structure of rhGH was determined using Fourier transform infrared (FTIR) spectroscopy. rhGH exhibited a decrease in alpha-helix and increase in beta-sheet structures upon drying. Addition of excipient stabilized the secondary structure upon lyophilization to a varying extent depending on the formulation. Samples with a significant degree of structural conservation, as indicated by the alpha-helix content, generally exhibited reduced aggregation. In addition, prevention of protein-protein interactions (indicated by reduced beta-sheet formation) also tended to result in lower rates of aggregation. Therefore, in addition to preserving the protein structure, bulk additives that do not crystallize easily and remain amorphous in the solid state can be used to increase protein-protein distance and thus prevent aggregation.

Drug Stability↗
PubMed1997

Spray dried powders and powder blends of recombinant human deoxyribonuclease (rhDNase) for aerosol delivery.

PURPOSE: We have used rhDNase to investigate the feasibility of developing a dry protein powder aerosol for inhalation delivery. METHODS: Powders of rhDNase alone and with sodium chloride were prepared by spray drying. Powder blends were obtained by mixing (tumbling and sieving) pure rhDNase powder with 'carrier' materials (lactose, mannitol or sodium chloride). The weight percent of drug in the blends was between 5 and 70%. The particle size distributions and crystallinity of the spray dried powders were obtained by laser diffraction and X-ray powder diffraction, respectively. Particle morphology was examined by scanning electron microscopy. The ability of the powders and powder blends to be dispersed into respirable aerosols was measured using a Rotahaler connected to a multistage liquid impinger operating at 60 L/min. RESULTS: Pure rhDNase powder was quite cohesive with a fine particle fraction (FPF or "respirable fraction': % wt. of particles < 7 microns in the aerosol cloud) of about 20%. When particles also contained NaCl, the powders were dispersed better to form aerosols. A linear relationship was observed between the NaCl content and FPF for a similar primary size (approximately 3 microns volume median diameter) of particles. The particle morphology of these powders varied systematically with the salt content. For the blends, SEM revealed a monolayer-like adhesion of the fine drug particles to the carriers at drug contents > or = 50% wt. An overall 2-fold increase in FPF of rhDNase in the aerosol cloud was obtained for all the blends compared to the pure drug aerosols. CONCLUSIONS: The aerosol properties of spray dried rhDNase powders can be controlled by incorporation of a suitable excipient, such as NaCl, and its relative proportion. Coarse carriers can also enhance the performance of rhDNase dry powder aerosols.

Aerosols↗
PubMed1997

[Physician and the patient with headache].

The chronicity of headache, the frequent consultations and the deceiving results of most headache treatments characterize the difficult relation of physicians with these patients. These particularities are discussed, and some recommendations for the relation with headache patients are given.

Attitude of Health Personnel↗
PubMed1997

[The dangerous headache].

Some particularities are frequent in headache types due to a potentially dangerous disease, namely sudden onset, rapid increase of pain intensity, very localized headache, increasing frequency and intensity of pain, and the insurgence of neurological or psychopathological signs. The headache types showing one of these characteristics are discussed in detail.

Aneurysm↗
PubMed1996

[Fellowship among physicians].

The relation among physicians is quite frequently characterized by conflicts. The different types of problems which may come up are discussed, and finally the author tries to formulate some rules which could improve the situation.

Conflict, Psychological↗
PubMed1996

[Migraine: diagnosis, differential diagnosis and treatment].

Headache takes a large place in daily medical practice, and it is important to try and establish the most precise possible diagnosis. An outline of the diagnosis and differential diagnosis of migraine is followed by a discussion of interval drug treatment forms and counselling. Today's recommended treatment for attacks and the commonest sources of error in migraine management are summarized.

Analgesics↗
PubMed1996

Alcohol elimination and simulator performance of male and female aviators: a preliminary report.

OBJECTIVES: In this preliminary study of alcohol effects on aviators' flight simulator performance, we addressed some methodological issues regarding possible gender-related differences in response to alcohol. METHODS: Subjects were 11 male and 12 female general aviation pilots, ages 21-40. Subjects received 8 h of training before they were tested with alcohol. On the alcohol test day they were tested before drinking, while intoxicated (target BAC of 0.08%), and 8 h after drinking. RESULTS: The average, observed peak BAC readings for men and women were within 0.003% of each other. We observed faster disappearance rates for women such that women reached the FAA cutoff of 0.04% approximately 1 h before men, on average. Compared to predrink performance, there was a significant decrement in simulator performance during acute intoxication, but not 8 h after drinking. There were no significant gender differences in performance before or after drinking alcohol. Slower rates of alcohol elimination were associated with larger performance changes 8 h after drinking. This is the first report to our knowledge suggesting a possible relation between alcohol elimination rate and change in performance after drinking alcohol. CONCLUSIONS: A 12.5% dose reduction for women appears to be adequate for achieving comparable peak BAC's for male and female groups. Future studies using measures of circadian rhythmicity in conjunction with pharmacokinetic and performance measures could potentially shed light on differences in subjects' acute and delayed responses to alcohol.

Adult↗
PubMed1994

[Syncope--incidence, diagnosis and differential diagnosis].

Syncopes are not rare at all. They are seen in 0.75% of patients of an outpatient department of internal medicine, and 0.03% of blood donors have syncopes. In the Framingham study, in the course of 26 years 3 to 3.6% of the population had syncopes. The diagnosis can be made just by careful questioning and the usual physical examination of the patient. In spite of thorough examination, the cause of the syncope cannot be determined in 25 to 85% of cases. Among those carefully analysed, 5 to 15% are due to a primary cerebral cause and 15 bis 40% are due to a cardiovascular problem. Of course selection of patients following the institution which made these studies play an important role. We conclude that the careful questioning of the patient and, if possible, of witnesses of the syncope represents the most important element for diagnosis.

Adolescent↗
PubMed1994

Feasibility study on spray-drying protein pharmaceuticals: recombinant human growth hormone and tissue-type plasminogen activator.

The feasibility of spray-drying solutions of recombinant methionyl human growth hormone (hGH) and tissue-type plasminogen activator (t-PA) was investigated. hGH was formulated in a mannitol phosphate buffer and t-PA was used in an arginine phosphate formulation containing 0.004% (w/v) polysorbate 80. Using filtered air (90-150 degrees C) as the drying medium, hGH could be dried to a residual moisture content of < or = 4%. However, approximately 25% of the protein was degraded during the processing. Results of atomization studies suggest that surface denaturation at the air-liquid interface of the droplets in the spray plays a major role in the degradation of the protein. The addition of 0.1% (w/v) polysorbate 20 into the hGH formulation reduced the formation of soluble and insoluble aggregates by approximately 90% during atomization. During spray-drying the addition of 0.1% (w/v) polysorbate 20 reduced the formation of soluble and insoluble aggregates by approximately 70 and 85%, respectively. In contrast, t-PA remained intact upon atomization. Depending on the spray-drying conditions, product powders with a residual moisture content between 5 and 8% were obtained. No oxidation, aggregation, or denaturation occurred in the protein under several operation conditions. Overall, this study demonstrates that it is feasible to spray-dry t-PA in the current marketed formulation.

Calorimetry, Differential Scanning↗
PubMed1993

[Results of a 1-year follow-up study of whiplash injury].

Based on a strict definition of whiplash injury, a sample of 117 non-selected patients was examined 7.2 +/- 4.2 days and at 3, 6 and 12 months after trauma. Initially all patients underwent a neurological examination, cognitive and psychosocial factor assessment and cervical spine x-rays. 56%, 70% and 76% of patients had completely recovered at 3, 6 and 12 months respectively. The results indicated that impairment of patients' well-being and cognitive ability was closely associated with somatic symptoms. No major impairment of attentional functioning was found, but some change in cognitive equilibrium was observed which may be related to the type of medication utilized. Delayed recovery at 12 months could be predicted by the following initial variables: higher age, intensity of initial neck pain and headache, symptoms of radicular irritation, sleep disturbances, pretraumatic headache, history of head trauma, nervousness score and--significantly inversely proportional--initial concentration problems and neuroticism score. These results suggest that a more severe neck injury may in particular account for delayed recovery from whiplash.

Adult↗
PubMed1993

[Shoulder-arm pain in routine general practice].

The anatomical basis of shoulder-arm-pain syndromes is described. One has to practise a multidisciplinary approach in order to correctly analyse shoulder-arm-pains. The most essential signs as well as the technique of examination of symptoms are described. The most frequent types of shoulder-arm-pain are subsequently mentioned.

Brachial Plexus Neuritis↗
PubMed1993

[Tarsal tunnel syndrome. Diagnosis and differential diagnosis].

The tarsal tunnel syndrome represents an entrapment neuropathy of the tibial nerve behind the internal malleolus under the retinaculum of the flexor muscles of the foot. In more than 3 out of 4 cases, it is a late consequence of twisting or fracture of the ankle. Local pain is increased by walking. In addition to local pain on pressure behind the internal malleolus, at a later stage paresis of the small foot muscles becomes evident with impaired abduction of the toes, decreased sensation and abnormally dry, smooth skin over the sole of the foot. The impairment of tibial nerve function can also be shown electrophysiologically. Surgical treatment is recommended for advanced cases.

Ankle Injuries↗