Search PubMed⌕ Search

Biomedical subjects

G Gatti

Publications and source records attributed to G Gatti.

At least 19 recordsLinked to original sources
PubMed2003

Pharmacokinetics and pharmacodynamics of nelfinavir administered twice or thrice daily to human immunodeficiency virus type 1-infected children.

We studied the pharmacokinetics and pharmacodynamics of nelfinavir administered 2 or 3 times per day to human immunodeficiency virus type 1 (HIV-1)-infected children receiving highly active antiretroviral therapy containing nelfinavir. The geometric mean trough concentrations of nelfinavir for the thrice- and twice-daily regimens were 1.55 mg/L and 1.11 mg/L, respectively (P=not significant). Nelfinavir concentrations did not correlate with total daily dose, dose per kilogram of weight, age, weight, previous protease inhibitor (PI) experience, or CD4(+) cell percentage. In the 25 PI-naive children, the virus load reductions at 24 weeks of treatment with the twice- and thrice-daily regimens were comparable. A significantly higher percentage of children in the twice-daily group had a trough concentration of nelfinavir of less than the inhibitory concentration of 95% (P=.042). The decrease in the virus load at 24 weeks of treatment was not correlated with the trough concentration of nelfinavir. The variability of trough concentrations was extremely high, particularly among recipients of the twice-daily regimen, resulting in a higher number of patients with subinhibitory concentrations of nelfinavir in this group.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Synthesis of new C-6 alkyliden penicillin derivatives as beta-lactamase inhibitors.

New penicillin, penicillin sulfone and sulfoxide derivatives bearing a C-6-alkyliden substituent were prepared. Their chemical synthesis, in vitro antibacterial activity and inhibition properties against two selected enzymes representing Class A and C beta-lactamases are reported. Compounds 3a-c, 7a-c were able to inhibit either TEM-1 (a Class A enzyme, from Escherichia coli) or P-99 (a Class C enzyme, from E. cloacae), or both enzymes, when tested in competition experiments using nitrocefin as the reporter substrate. However, when tested in combination with amoxicillin, the same compounds did not show synergistic effects against E. coli and E. cloacae strains producing TEM-1 and P99 enzymes, respectively. This finding is most likely related to poor penetration through the bacterial cell wall, as shown by using a more permeable isogenic E. coli strain. Interestingly, a synergistic effect against a strain of S. aureus which produces PC1-enzyme (a Class A beta-lactamase) was observed for compound 3a when used in combination with amoxicillin.

Amoxicillin↗
PubMed2002

Heparin reversal in off-pump coronary artery bypass surgery: complete, partial, or no reversal?

Several clinical studies have reported that avoiding cardiopulmonary bypass reduces postoperative bleeding. The purpose of this study is to verify that protamine during off-pump coronary artery bypass surgery produces significant reduction of postoperative bleeding. Sixty consecutive patients undergoing off-pump coronary artery bypass surgery were prospectively randomized in three groups: Group A received 1 mg of protamine every 100 IU of heparin, Group B 0.5 mg of protamine every 100 IU of heparin, and Group C none. The three groups were analyzed for differences in preoperative cardiac function, pre-, intra-, and postoperative coagulation profile, intraoperative variables, and postoperative bleeding. In the three study groups, no statistically significant difference was found in preoperative cardiac function, pre- and intraoperative coagulation profile, and prothrombin time, activated partial thromboplastin time, platelet count in the first postoperative day. In Group A, total postoperative bleeding, use of packed red blood cells, and mild pericardial effusion prevalence at discharge were significantly lower only when compared to Group C, but they were not significantly different when compared to Group B. In off-pump coronary artery bypass surgery, heparin should be reverted with protamine, otherwise the postoperative bleeding risk might increase. Partial heparin reversal might not increase postoperative bleeding risk, but it may reduce dose-dependent protamine adverse effects.

Aged↗
PubMed2002

The relationship between ritonavir plasma trough concentration and virological and immunological response in HIV-infected children.

BACKGROUND: We studied a number of factors, including ritonavir plasma levels, and their capability of predicting response to therapy with ritonavir (RTV). METHODS: Eleven HIV-positive children, nucleoside reverse transcriptase inhibitor (NRTI)-experienced, protease inhibitor (PI) naive, receiving RTV in combination with two NRTIs were enrolled in the study. Demographic parameters were: median age (range) 10 (2-13) years, weight 26 (10-38) kg, body surface area (BSA) 0.93 (0.47-1.21) m(2). Baseline values of CD4, percent CD4 and viral load were 137 (2-1390) cells/microL, 9.5 (0.4-32.4)%, and 5.15 (4.30-6.18) log10 copies/mL, respectively. The dose of RTV was 318 (266-409) mg/m(2) twice daily. Peak (3.5 h after administration) and trough (predose) plasma concentrations of RTV were determined on one occasion at steady-state after a morning dose. Virological response to treatment was quantified as the difference between the baseline value of viral load and the value observed at 6 months of therapy (Delta(6)). RESULTS: The relationship between Delta(6) and demographic parameters (age, weight, BSA, and baseline CD4, percent CD4, and viral load) and plasma concentrations of RTV was studied by linear regression. Median (range) Delta(6) was 0.88 (0.77-2.62) log10 copies/mL. Peak and trough of RTV were 14.9 (3.2-31.4) and 5.0 (0.1-15.6) mg/L, respectively. Trough concentration of RTV was the best predictor of Delta(6), although the relationship between these two variables was not statistically significant (r = 0.56, P = 0.075). CONCLUSION: Our observation of a trend for a greater decrease in viral load in patients with higher trough concentration of RTV warrants further pharmacodynamic studies of PI in paediatric patients.

Area Under Curve↗
PubMed2001

The impact of human immunodeficiency virus type 1 on infectiousness of tuberculosis: a meta-analysis.

To assess if the relative infectiousness of patients with tuberculosis is enhanced by coinfection with human immunodeficiency virus type 1 (HIV-1), data from 6 studies of 1240 health care workers who had contact with tuberculosis patients were analyzed. Overall rates of tuberculin skin test conversion were similar regardless of HIV-1 positivity of tuberculosis patients (odds ratio [OR], 1.04; 95% confidence interval [CI], 0.23-1.84). However, when only 3 studies during nosocomial outbreaks of multidrug-resistant Mycobacterium tuberculosis were analyzed, rates of skin test conversion were higher among contacts of HIV-1-positive index cases (OR, 2.85; 95% CI, 1.85-3.85; P=.0002). A second meta-analysis included data from 11 studies of 10,714 household contacts of tuberculosis patients. Prevalence of both skin test positivity (OR, 0.45; 95% CI, 0.20-1.03) and active disease (OR, 1.17; 95% CI, 0.78-1.56) were similar regardless of HIV-1 positivity of index cases. These data suggest that tuberculosis patients with HIV-1 infection are not intrinsically more infectious to their contacts than are HIV-1-negative tuberculosis patients.

AIDS-Related Opportunistic Infections↗
PubMed2001

Head-to-tail oligomerization of calsequestrin: a novel mechanism for heterogeneous distribution of endoplasmic reticulum luminal proteins.

Many proteins retained within the endo/sarcoplasmic reticulum (ER/SR) lumen express the COOH-terminal tetrapeptide KDEL, by which they continuously recycle from the Golgi complex; however, others do not express the KDEL retrieval signal. Among the latter is calsequestrin (CSQ), the major Ca2+-binding protein condensed within both the terminal cisternae of striated muscle SR and the ER vacuolar domains of some neurons and smooth muscles. To reveal the mechanisms of condensation and establish whether it also accounts for ER/SR retention of CSQ, we generated a variety of constructs: chimeras with another similar protein, calreticulin (CRT); mutants truncated of COOH- or NH2-terminal domains; and other mutants deleted or point mutated at strategic sites. By transfection in L6 myoblasts and HeLa cells we show here that CSQ condensation in ER-derived vacuoles requires two amino acid sequences, one at the NH2 terminus, the other near the COOH terminus. Experiments with a green fluorescent protein GFP/CSQ chimera demonstrate that the CSQ-rich vacuoles are long-lived organelles, unaffected by Ca2+ depletion, whose almost complete lack of movement may depend on a direct interaction with the ER. CSQ retention within the ER can be dissociated from condensation, the first identified process by which ER luminal proteins assume a heterogeneous distribution. A model is proposed to explain this new process, that might also be valid for other luminal proteins.

Amino Acid Sequence↗
PubMed2001

[Intraoperative radiotherapy (IORT) in treatment of breast carcinoma--a new therapeutic alternative within the scope of breast-saving therapy? Current status and future prospects. Report of experiences from the European Institute of Oncology (EIO), Mailand].

BACKGROUND: External beam radiation therapy (EBRT) represents an integral component of breast-conserving treatment. In published series it has been demonstrated that the external boost can be replaced by intraoperative radiotherapy (IORT) where irradiation at a single dose from 10 up to 15 Gy was safely delivered directly to the tumor bed. PATIENTS AND METHODS: At the European Institute of Oncology, Milan, we initiated a dose escalation study to investigate the feasibility of applying single doses of IORT from 10 Gy up to 22 Gy. A portable IORT equipment with different electron energies was used. From July to December 1999, a total of 65 patients with T1-2 (max. 2.5 cm) No-1 breast cancer, median age 58 years (range 33-80 years) was treated. Ten patients received 10 Gy, eight patients were treated with an IORT of 15 Gy, eight received 17 Gy, six had 19 Gy, and 33 were treated with 21-22 Gy. Patients with 10 and 15 Gy received an additional EBRT of 44 and 40 Gy, respectively. In all other patients IORT was the sole radiation treatment. RESULTS: No acute side effects or intermediate untoward effects after a follow-up from three to nine months related to IORT were observed. CONCLUSIONS: Since the applicator can be safely placed under the control of the surgeon and radiotherapist IORT has the potential of accurately treating the tumor bed. Skin and subcutaneous tissue are not irradiated thus decreasing the potential risk of fibrosis and eventually obtaining a better cosmesis. With IORT single doses of 22 Gy being equivalent to a 60 Gy EBRT can safely be delivered. Even so the average time of operation was prolonged by around 20 minutes IORT application ultimately improves the quality of life of the patients in shortening overall treatment. Long-term follow-up is necessary to demonstrate whether large single doses of IORT might have the potential of sufficient local tumor control without major side effects. As a future perspective a randomized trial comparing EBRT with IORT as sole treatment will be performed.

Adult↗
PubMed2001

Tricuspid valve repair with the Cosgrove-Edwards annuloplasty system: early clinical and echocardiographic results.

BACKGROUND: The use of flexible rings for tricuspid valve repair is becoming popular. The purpose of this study was to evaluate the Cosgrove-Edwards annuloplasty system for tricuspid regurgitation. METHODS: From June 1998 to December 2000, 22 patients with significant secondary tricuspid regurgitation underwent tricuspid valve repair with the Cosgrove-Edwards annuloplasty system. All patients had disease of left-sided heart valves in addition to tricuspid disease; 34 concomitant procedures were performed. Twenty-one patients (95.5%) were in preoperative New York Heart Association functional class 3 or 4. The mean follow-up was 19.9 +/- 9.7 months. RESULTS: There were two in-hospital nonvalve-related cardiac deaths (9.1%) and one noncardiac death after discharge (4.5%). All survivors were in New York Heart Association functional class 1 or 2; their tricuspid regurgitation was well controlled within grade 1+ and there was a significant reduction of systolic pulmonary artery pressure. Five (83.3%) of the 6 survivors with preoperative pulmonary hypertension had no or trivial residual tricuspid regurgitation. CONCLUSIONS: The Cosgrove-Edwards annuloplasty system is very effective in the treatment of secondary tricuspid regurgitation, also in the presence of pulmonary hypertension.

Adult↗
PubMed2001

A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated.

Local recurrences after breast conserving surgery occur mostly in the quadrant harbouring the primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area, while irradiation of the whole breast may be avoided. We have developed a new technique of intra-operative radiotherapy (IORT) of a breast quadrant after the removal of the primary carcinoma. A mobile linear accelerator (linac) with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Through a perspex applicator, the radiation is delivered directly to the mammary gland and to spare the skin from the radiation, the skin margins are stretched out of the radiation field. To protect the thoracic wall, an aluminium-lead disc is placed between the gland and the pectoralis muscle. Different dose levels were tested from 10 to 21 Gy without important side-effects. We estimated that a single fraction of 21 Gy is equivalent to 60 Gy delivered in 30 fractions at 2 Gy/fraction. Seventeen patients received a dose of IORT of 10 to 15 Gy as an anticipated boost to external radiotherapy, while 86 patients received a dose of 17-19-21 Gy intra-operatively as their whole treatment. The follow-up time of the 101 patients varied from 1 to 17 months (mean follow-up time was 8 months). The IORT treatment was very well accepted by all of our patients, either due to the rapidity of the radiation course in cases where IORT was given as the whole treatment or to the shortening of the subsequent external radiotherapy in cases where IORT was given as an anticipated boost. We believe that single dose IORT after breast resection for small mammary carcinomas may be an excellent alternative to the traditional postoperative radiotherapy. However, a longer follow-up is needed for a better evaluation of the possible late side-effects.

Adult↗
PubMed2001

Are clinicians correct when they believe they are correct? Implications for medical decision support.

The process of clinical decision support is linked to the validity of clinicians' confidence in their judgments. Clinicians who are appropriately confident-highly confident when they are correct and less confident when they are incorrect-will access computer-based and other information resources only when they are needed. Clinicians who are consistently underconfident will rely on external resources when they are not needed. Those who are overconfident, who believe they are correct when in fact they are not, will be prone to medical errors. An extensive literature indicates a general tendency toward overconfidence in human judgment. This study explores the relationship between confidence and "correctness", across three levels of clinical experience, in the task domain of diagnosis in internal medicine. We created detailed synopses of 36 diagnostically challenging cases and divided them into four equivalent sets of nine cases each. We asked 216 subjects at three experience levels (72 senior medical students, 72 senior medical residents, and 72 faculty attendings) to generate a differential diagnosis for each of the nine cases in one randomly-assigned set, and simultaneously to indicate their level of confidence in each of their diagnoses. We then examined the relationship between the correctness of these diagnoses (the appearance of the correct diagnosis anywhere in the hypothesis list) and these confidence judgments, for all subjects and separately for subjects at each experience level. Results indicate a small but statistically significant relationship associating correctness with higher confidence for all subjects (Kendall's tau b =.-106;p <.0001). This statistical relationship is strongest for the students ( tau b =.-121;p <.001), somewhat lesser but still significant for the faculty-level attendings ( tau b =.-103;p <.005), and non-significant ( tau b =.-041 ) for the residents. (The negative correlations are a coding artifact.) Subjects in this study showed a tendency toward underconfidence: they had low confidence in correct diagnoses more often than they had high confidence when wrong. Nonetheless, they were overconfident and thus "error prone" for 17% of cases overall. The medical students were possibly overmatched by the difficulty of the cases, so their concordance between confidence and correctness may have resulted from an awareness that they were often guessing. The relatively low concordance seen in the residents and attendings makes a strong argument that decision support systems to reduce medical errors should include both "push" and "pull" models. In sum, these results indicate that medical decision support systems cannot rely exclusively on clinicians' perceptions of their information needs, as such perceptions will frequently be incorrect.

Clinical Medicine↗
PubMed2001

[Continence problems after radical prostatectomy: role of rehabilitation of the pelvic floor].

Continence mechanisms can be compromised after radical prostatectomy. Relatively low percentages of urinary incontinence are reported (2-15%). Perineal floor physiotherapy is considered an actual method of treatment of urinary incontinence in females. It is based on pelvic floor muscles exercises, biofeedback and functional electrical stimulation. The aim of physiotherapy is to improve pelvic floor muscles proprioception, to increase tone of levator ani and to favour automatization of these muscles in daily life. The reports in Literature on perineal floor physiotherapy in treating incontinence after radical prostatectomy are scarce. In this paper we present our experience about 9 patients with incontinence post radical prostatectomy (out of 74 patients operated on at our Institution). We obtained an improvement or a complete cure in 78% of the treated patients. We believed that pelvic floor physiotherapy can be considered a good and safe method of treatment of incontinence after radical prostatectomy, at least in less serious cases.

Aged↗
PubMed2000

A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy.

PURPOSE: To assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy. METHODS: One-hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel-group design. In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds. Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated. RESULTS: Baseline characteristics did not differ between the two groups. Most patients with partial epilepsy were treated with CBZ, whereas generalized epilepsies were most commonly managed with PB or VPA. PHT was used only in a small minority of patients. A total of 116 patients completed 2-year follow-up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable patients with mean serum drug levels outside the target range (mostly below range) during the first 6 months of the study was 8% in the monitored group compared with 25% in the control group (p < 0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12-month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to first seizure or 12-month remission. Frequency of adverse effects was almost identical in the two groups. CONCLUSIONS: Only a small minority of patients were treated with PHT, the drug for which serum concentration measurements are most likely to be useful. With the AEDs most commonly used in this study, early implementation of serum AED level monitoring did not improve overall therapeutic outcome. and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than routine measurements in a large clinic population.

Adolescent↗
PubMed2000

Indinavir pharmacokinetics and parmacodynamics in children with human immunodeficiency virus infection.

The indinavir dosage regimen currently used for human immunodeficiency virus (HIV)-infected children is not based on pharmacokinetic data obtained in the target patient population. The purpose of our study was to characterize indinavir pharmacokinetics and pharmacodynamics in HIV-infected children. Eleven children (age range, 9.0 to 13.6 years; weight range, 21.7 to 56.0 kg) receiving indinavir (500 mg/m(2) every 8 h) in combination with lamivudine and stavudine were studied. The correlation of indinavir pharmacokinetic parameters and demographic parameters was evaluated. Also, the pharmacodynamic relationship between parameters of indinavir exposure and parameters of renal toxicity and immunologic recovery was studied. The area under the indinavir concentration-time curve (AUC) and patient body surface area (BSA) showed a significant negative correlation (r = 0.73; P = 0.012). Patients with smaller BSA had excessive indinavir AUC compared to adults. On the other hand, the median minimum drug concentration in plasma (C(min)) was lower than that reported for adults. The maximum indinavir concentration in serum was higher in patients with renal toxicity (5 out of 11 children), but the difference was not statistically significant (15.3 +/- 8.2 versus 9.8 +/- 4.4 mg/liter; P = 0.19). There was a trend toward higher immunologic efficacy in patients with greater indinavir exposure: the time-averaged AUC of the percentage of CD4(+) lymphocytes over the baseline value for patients with indinavir C(min) > 95% inhibitory concentration (IC(95)) was higher than in patients with C(min) < IC(95) (P = 0. 068). Our study suggests that a dose reduction may be appropriate for children with small BSA and that a 6-h dosage regimen may be indicated for a substantial percentage of patients. Due to the low number of patients enrolled in this study, our results should be confirmed by a larger study.

Adolescent↗
PubMed2000

The new antiepileptic drugs: pharmacological and clinical aspects.

In recent years several new drugs (oxcarbazepine, lamotrigine, topiramate, gabapentin, zonisamide, tiagabine, fosphenytoin, vigabatrin and felbamate) have been added to the therapeutic armamentarium against epilepsy. Some of these represent structural modifications of pre-existing compounds, others were developed with the specific objective of modifying neurotransmitter function, and many more were found to be clinically useful even though their mode of action is unclear or differs from that originally planned. The pharmacokinetics of these drugs differ widely from one agent to another. Some (gabapentin and vigabatrin) are eliminated unchanged in urine and have little or no interaction potential; others (tiagabine, lamotrigine, topiramate, oxcarbazepine, zonisamide, felbamate) are subject to induction of metabolism by concomitant anticonvulsants; lamotrigine is vulnerable to metabolic inhibition by valproate, and felbamate is a powerful enzyme inhibitor in addition to being an inducer of the metabolism of carbamazepine and steroid oral contraceptives. All new antiepileptic drugs have been found to be effective in improving seizure control in patients with partial and secondarily generalized seizures. However, lamotrigine, topiramate, zonisamide and felbamate appear to have broader efficacy against both partial and many generalized seizure types, while vigabatrin is also valuable in the management of infantile spasms. In monotherapy studies, new drugs have not been found to be more efficacious than older agents, but some may offer limited advantages in terms of improved tolerability. On the other hand, serious toxicity restricts considerably the use of vigabatrin and felbamate. Overall, new drugs represent valuable tools in the fight against epilepsy, but because of limited experience and cost considerations their first-line use cannot be recommended in most situations.

Animals↗
PubMed2000

A case of dengue from Pune, India.

Dengue is an acute infectious disease, caused by a single stranded ribonucleic acid (RNA) virus of the family of Flaviviridae, genus Flavivirus, transmitted by Aedes mosquitos, the most important vectors being Aedes aegypti and Aedes albopictus. There are four serotypes, DEN-1, DEN-2, DEN-3, DEN-4 that are nearly human specific. The geographical distribution of dengue is pantropical, except for Madagascar and some African regions. It is endemo-epidemic in tropical and subtropical countries included between 25 degrees north latitude and 25 degrees south latitude, particularly in southeast Asia and epidemic in the Caribbean, West-Africa, tropical American and Pacific Islands. Further spread will depend on the invasion of Aedes aegypti into new areas in South America. Maintenance of dengue is supported by an increasing demography, uncontrolled urbanization and climatic conditions favorable to the vectors. Spread of dengue is primarily caused by modern transportation, especially aircraft. No vaccine and no specific treatment exist so that mosquito control is the only way to reduce the incidence of dengue around the world. Dengue is, obviously, an important risk for travelers going to endemic areas.

Adult↗
PubMed1999

The contribution of magnetic resonance imaging to the three-dimensional treatment planning of localized prostate cancer.

PURPOSE: To investigate whether the use of transaxial and coronal MR imaging improves the ability to localize the apex of the prostate and the anterior part of the rectum compared to the use of transaxial CT alone, and whether the incorporation of MR could improve the coverage of the prostate by the radiotherapy field and change the volume of rectum irradiated. METHODS AND MATERIALS: Ten consecutive patients with localized prostate carcinoma underwent a CT and an axial and coronal MR scan in treatment position. The CT and MR images were mathematically aligned, and three observers were asked to contour independently the prostate and the rectum on CT and on MR. The interobserver variability of the prostatic apex location and of the delineation of the anterior rectal wall were assessed for each image modality. A dosimetry study was performed to evaluate the dose to the rectum when MR was used in addition to CT to localize the pelvic organs. RESULTS: The interobserver variation of the prostatic apex location was largest on CT ranging from 0.54 to 1.07 cm, and smallest on coronal MR ranging from 0.17 to 0.25 cm. The interobserver variation of the delineation of the anterior rectum on MR was small and constant along the whole length of the prostate (0.09+/-0.02 cm), while for CT it was comparable to that for the MR delineation at the base of the prostate, but it increased gradually towards the apex, where the variation reached 0.39 cm. The volume of MR rectum receiving more than 80% of the prescribed dose was on average reduced by 23.8+/-11.2% from the CT to the MR treatment plan. CONCLUSION: It can be concluded that the additional use of axial and coronal MR scans, in designing the treatment plan for localized prostate carcinoma, improves substantially the localization accuracy of the prostatic apex and the anterior aspect of the rectum, resulting in a better coverage of the prostate and a potential to reduce the volume of the rectum irradiated to a high dose.

Dose-Response Relationship, Radiation↗